Information on EC 3.5.3.1 - arginase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
3.5.3.1
-
RECOMMENDED NAME
GeneOntology No.
arginase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-arginine + H2O = L-ornithine + urea
show the reaction diagram
thermodynamic data
-
L-arginine + H2O = L-ornithine + urea
show the reaction diagram
also hydrolyses alpha-N-substituted L-arginines and canavanine
-
L-arginine + H2O = L-ornithine + urea
show the reaction diagram
Asn130 and Ser137 are involved in substrate binding and catalysis
-
L-arginine + H2O = L-ornithine + urea
show the reaction diagram
hydrolysis via a metall-activated hydroxide mechanism, substrate binding structure
-
L-arginine + H2O = L-ornithine + urea
show the reaction diagram
substrate binding structure
-
L-arginine + H2O = L-ornithine + urea
show the reaction diagram
H141 as general acid to protonate the leaving amino group of L-ornithine during catalysis
P05089
L-arginine + H2O = L-ornithine + urea
show the reaction diagram
H141 serves as an acid/base catalyst, deprotonating the metal-bridging water molecule to generate the metal-bridging hydroxide nucleophile, and by protonating the amino group of the product to facilitate its departure
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of linear amidines
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Arginine and proline metabolism
-
-
arginine metabolism
-
-
Biosynthesis of antibiotics
-
-
Biosynthesis of secondary metabolites
-
-
canavanine degradation
-
-
L-arginine degradation I (arginase pathway)
-
-
L-arginine degradation VI (arginase 2 pathway)
-
-
L-arginine degradation VII (arginase 3 pathway)
-
-
L-citrulline biosynthesis
-
-
L-Ndelta-acetylornithine biosynthesis
-
-
Metabolic pathways
-
-
putrescine biosynthesis IV
-
-
urea cycle
-
-
urea cycle
-
-
SYSTEMATIC NAME
IUBMB Comments
L-arginine amidinohydrolase
Also hydrolyses alpha-N-substituted L-arginines and canavanine.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
arginine amidinase
-
-
-
-
arginine transamidinase
-
-
-
-
canavanase
-
-
-
-
Kidney-type arginase
-
-
-
-
L-arginase
-
-
-
-
Liver-type arginase
-
-
-
-
Non-hepatic arginase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9000-96-8
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
ecotype Columbia
-
-
Manually annotated by BRENDA team
Bacillus anthracis 7702
7702
-
-
Manually annotated by BRENDA team
Bacillus brevis Nagano
-
-
-
Manually annotated by BRENDA team
Bacillus brevis TT02-8
-
-
-
Manually annotated by BRENDA team
adult cow
-
-
Manually annotated by BRENDA team
Capra capra
-
-
-
Manually annotated by BRENDA team
and highly homologous sequence variants Q4A3J1, Q4A3J0, isoform arginase II; isoform arginase II
SwissProt
Manually annotated by BRENDA team
and highly homologous sequence variants Q4A4U9, Q4A3J0, isoform arginase II; isoform arginase II
SwissProt
Manually annotated by BRENDA team
and highly homologous sequence variants Q4A4U9, Q4A3J1, isoform arginase II; isoform arginase II
SwissProt
Manually annotated by BRENDA team
isoform arginase I; isoform arginase I
SwissProt
Manually annotated by BRENDA team
fruit bat
-
-
Manually annotated by BRENDA team
enzyme additionally shows lectin function, binding to the cell wall of both homologous and heterologous algae
-
-
Manually annotated by BRENDA team
isoforms arginase-I and arginase-II
-
-
Manually annotated by BRENDA team
Glycine hispida
var. Cheepewa
-
-
Manually annotated by BRENDA team
; strain 43504, gene rocF
-
-
Manually annotated by BRENDA team
Helicobacter pylori 43504
strain 43504, gene rocF
-
-
Manually annotated by BRENDA team
2 isoenzymes
-
-
Manually annotated by BRENDA team
control and physician-diagnosed asthma patients
-
-
Manually annotated by BRENDA team
control and physician-diagnosed asthma patients
UniProt
Manually annotated by BRENDA team
isoform arginase I
UniProt
Manually annotated by BRENDA team
isoform arginase II
-
-
Manually annotated by BRENDA team
isoforms arginase-I and arginase-II
-
-
Manually annotated by BRENDA team
isozyme II
-
-
Manually annotated by BRENDA team
isozyme type II
-
-
Manually annotated by BRENDA team
outpatients with sickle cell disease
-
-
Manually annotated by BRENDA team
patients with cystic fibrosis, before and after 14 days of antibiotic treatment for pulmonary exacerbation
-
-
Manually annotated by BRENDA team
patients with histologically proven carcinoma of the gallbladder and 20 patients with cholecystitis
-
-
Manually annotated by BRENDA team
patients with liver cirrhosis or metastatic tumors
UniProt
Manually annotated by BRENDA team
recombinat isoform arginase I
-
-
Manually annotated by BRENDA team
overview
-
-
Manually annotated by BRENDA team
gray
-
-
Manually annotated by BRENDA team
hybrid B6/129
-
-
Manually annotated by BRENDA team
normal and nitric oxide synthase 2-knockout mice
-
-
Manually annotated by BRENDA team
ovalbumin-sensitized Balb/c mice
-
-
Manually annotated by BRENDA team
Mus musculus B6/129
hybrid B6/129
-
-
Manually annotated by BRENDA team
multiple forms
-
-
Manually annotated by BRENDA team
no activity in Sus scrofa
in enterocytes of suckling piglets or in rapidly growing porcine placentae
-
-
Manually annotated by BRENDA team
oopherectomized animals treated with 0.5% cholesterol-enriched diet. Diet results in increase in plasma lipids, atheromatous lesions as well as expression of enzyme isoforms arginase I and II and an increase in cellular proliferation. Diet plus supplementation of 17beta-estradiol results in a decrease of atheromatous lesions and reduced expression of both enzyme isoforms and inducible NO synthase
-
-
Manually annotated by BRENDA team
precursor
UniProt
Manually annotated by BRENDA team
white New Zealand rabbits, isozyme II
-
-
Manually annotated by BRENDA team
Pista pacifica
-
-
-
Manually annotated by BRENDA team
recombinant enzyme
-
-
Manually annotated by BRENDA team
Sprague-Dawley rat, fetus, newborn, adult
UniProt
Manually annotated by BRENDA team
Rhodobacter capsulatus E1F1
E1F1
-
-
Manually annotated by BRENDA team
isoform LeARG1; enzyme isoform LeARG1
SwissProt
Manually annotated by BRENDA team
isoform LeARG2; isoform LeARG2
SwissProt
Manually annotated by BRENDA team
with hypertension due to aortic coarctation
-
-
Manually annotated by BRENDA team
Vigna catjang
-
-
-
Manually annotated by BRENDA team
enzyme additionally shows lectin function, binding to the cell wall of both homologous and heterologous algae
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
-
the disulfide bond is important for the overall stability and folding of the protein. Mutant proteins lacking the disulfide bond start to unfold at lower temperature than the wild-type. In the mutant proteins, the Tm of the holoenzyme is 4C higher than that of the apoenzyme indicating that in the absence of the disulfide bond the metal ions have relatively larger role in the stability of the mutant proteins compared to the wild-type
physiological function
Mammalia, Capra capra
-
regulating synthesis of nitric oxide, proline, polyamine
physiological function
-
ARG1 and ARG2 are enzymatically active in hormone-sensitive and hormone-refractory prostate cancer cell lines and their decreased expression by siRNA results in reduced overall arginase activity and L-arginine metabolism. The decreased ARG1 and ARG2 expression also translates with diminished LNCaP cells cell growth and increased peripheral blood mononuclear cell activation following exposure to LNCaP cells conditioned media. Interleukin-8 is also upregulated following androgen stimulation and it directly increases the expression of ARG1 and ARG2 in the absence of androgens
physiological function
-
coinhibitory and costimulatory molecules PD-1 and CTLA-4 on the Gr-1+CD11b+ myeloid-derived suppression cells regulate the activity and expression of arginase I. The blockage and silencing of PD-1, CTLA-4 or both PD-1 and CTLA4 molecules can significantly reduce arginase I activity and expression induced with tumor-associated factor. Similar results are also observed while their ligands B7-H1 and/or CD80 are blocked or silenced. CD80 deficiency also decreases the arginase I expression and activity. Antibody blockade or silencing of PD-1, CTLA-4 or both reduces the suppressive potential of PD-1+CTLA-4+ myeloid-derived suppression cells. Blockade of PD-1, CTLA-4 or both also slows tumor growth and improves the survival rate of tumor-bearing mice
physiological function
-
comparison of the infectivity of arg- and wild-type Plasmodium berghei by inoculation of mice using sporozoites dissected from mosquito salivary glands shows a significant reduction in infectivity in the arg- strain 40 h postinfection
physiological function
-
in arginase I-deficient bone marrow chimeric mice, following transfer of arginase I-deficient bone marrow into irradiated recipient mice, arginase I expression is not required for hematopoietic reconstitution and baseline immunity. Arginase I deficiency in bone marrow-derived cells decreases allergen-induced lung arginase by 85.8%. Arginase II-deficient mice have increased lung arginase activity following allergen challenge to a similar level to wild type mice. Bone-marrow-derived arginase I is not required for allergen-elicited sensitization, recruitment of inflammatory cells in the lung, and proliferation of cells. Allergen-induced airway hyperresponsiveness and collagen deposition are similar in arginase-deficient and wild type mice. Arginase II-deficient mice respond similarly to their control wild type mice with allergen-induced inflammation, airway hyperresponsiveness, proliferation and collagen deposition
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1-nitro-3-guanidinobenzene + H2O
3-nitrobenzenamine + urea
show the reaction diagram
-
synthetic chromophoric substrate, low activity
-
-
?
4-guanidino-2-nitrophenylacetic acid + H2O
4-amino-2-nitrophenylacetate + urea
show the reaction diagram
-
-
-
-
?
4-guanidino-3-nitrobenzoic acid + H2O
4-amino-3-nitrobenzoate + urea
show the reaction diagram
-
-
-
-
?
agmatine + H2O
1,4-diaminobutane + urea
show the reaction diagram
Vigna catjang
-
16% of the activity with L-arginine
-
-
?
agmatine + H2O
1,4-diaminobutane + urea
show the reaction diagram
-
for wild-type, no substrate. Hydrolysis by mutant N149D
-
-
?
agmatine + H2O
1,4-diaminobutane + urea
show the reaction diagram
Q5UNS1, Q5UNS2
isoform LeARG1, 0.5% of the activity with L-arginine, LeARG2, 0.6% of the activity with L-arginine
-
-
?
argininic acid + H2O
urea + 5-amino-2-hydroxypentanoate
show the reaction diagram
-
-
-
-
?
canavanine + H2O
urea + NH2OCH2CH2CH(NH2)COOH
show the reaction diagram
-
-
-
-
?
canavanine + H2O
urea + NH2OCH2CH2CH(NH2)COOH
show the reaction diagram
Glycine hispida
-
-
-
-
?
canavanine + H2O
urea + NH2OCH2CH2CH(NH2)COOH
show the reaction diagram
Bacillus brevis TT02-8
-
-
-
-
?
canavanine + H2O
urea + NH2OCH2CH2CH(NH2)COOH
show the reaction diagram
Vigna catjang
-
12.7% of the activity with L-arginine
-
-
?
canavanine + H2O
urea + NH2OCH2CH2CH(NH2)COOH
show the reaction diagram
-
9.6% of the activity with L-arginine
-
-
?
D-arginine + H2O
D-ornithine + urea
show the reaction diagram
Q5UNS1, Q5UNS2
isoform LeARG1, 2.2% of the activity with L-arginine, LeARG2, 3.6% of the activity with L-arginine
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
P05089
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
ir
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
ir
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Glycine hispida
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Pista pacifica
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Bacillus brevis Nagano
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Bacillus brevis TT02-8
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Vigna catjang
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Q5UNS1, Q5UNS2
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Q4VK78
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
O08701, P07824
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
P78540
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Q6TA39
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Q8I384
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
enzyme is involved in acid resistance and inhibits host nitric oxide production
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
enzyme is involved in net production of ornithine, a precursor of polyamines, glutamate, and proline, enzyme is also involved in regulation of nitric oxide biosynthesis by modulating arginine availability for nitric oxide synthase
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
enzyme is involved in regulating L-arginine bioavailability to NO synthase in human penile corpus cavernosum smooth muscle, and in clitoral corpus cavernosum and vagina, enzyme plays a role in both female and male sexual arousal
-
-
ir
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
enzyme is involved in regulation of nitric oxide biosynthesis by modulating arginine availability for nitric oxide synthase
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
reaction intermediate is Nomega-hydroxy-L-arginine
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
arginase competes with nitric oxide synthases for L-arginine as the common substrate
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
assay at pH 7.4, 37C
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Helicobacter pylori 43504
-
enzyme is involved in acid resistance and inhibits host nitric oxide production
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Rhodobacter capsulatus E1F1
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Bacillus anthracis 7702
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Mus musculus B6/129
-
-
-
-
?
L-arginine + H2O
?
show the reaction diagram
-
-
-
-
-
L-arginine + H2O
L-ornithine
show the reaction diagram
-
-
-
-
?
L-homoarginine + H2O
L-2,6-diaminohexanoate + urea
show the reaction diagram
Q5UNS1, Q5UNS2
isoform LeARG1, 14% of the activity with L-arginine, LeARG2, 13% of the activity with L-arginine
-
-
?
p-nitrophenyl glyoxal + arginine
?
show the reaction diagram
-
-
-
-
?
S-(4-aminobutyl)isothiourea + H2O
?
show the reaction diagram
-
-
-
-
?
thioguanidino-valeric acid + H2O
?
show the reaction diagram
-
-
-
-
?
L-thioarginine + H2O
(2S)-2-amino-5-mercaptopentanoate + urea
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
isozyme selectivity in binding and substrate, products, and inhibitors
-
-
-
additional information
?
-
-
enzyme may be involved in cellular proliferation in atherosclerosis, inhibiton of enzyme expression by 17beta-estradiol as mechanism in attenuating atherogenensis
-
-
-
additional information
?
-
-
mitochondrial isoform arginase II negatively regulates NO synthase 1 activity by limiting substrate availability in its microdomain
-
-
-
additional information
?
-
-
presence of arginine pools, which are accessible to NO synthase and enzyme, but not exchangeable
-
-
-
additional information
?
-
-
no substrate: agmatine, D-arginine, L-homoarginine, L-argininic acid, gamma-guanidinobutyric acid, beta-guanidinopropionic acid, streptomycin
-
-
-
additional information
?
-
Vigna catjang
-
no substrate: D-arginine, L-homoarginine, L-argininic acid, gamma-guanidinobutyric acid, beta-guanidinopropionic acid, streptomycin
-
-
-
additional information
?
-
-
the wild type enzyme does not hydrolyze 1-amino-4-guanidinobutane (agmatine)
-
-
-
additional information
?
-
-
arginase II is constitutively expressed in the airways of normal mice, whereas arginase I is undetectable in normal airways, while its expression is increased in airways of mice exposed to ovalbumin
-
-
-
additional information
?
-
-
complex regulation of natural killer cell functions by arginine availability
-
-
-
additional information
?
-
P78540
hereditary defects in arginase compromise structure and catalysis, which results in an accumulation of arginine in the blood known as hyperarginemia. Arginase deficiency can also result in the accumulation of nitrogen in the form of ammonia, which results in hyperammonemia
-
-
-
additional information
?
-
Q6TA39
infection of mice with Schistosoma mansoni cercariae elevates arginase activity
-
-
-
additional information
?
-
-
recombinant human arginase I (rhArg-PEG), an arginine-depleting enzyme, can inhibit the growth of arginine-dependent tumors
-
-
-
additional information
?
-
-
model cluster used to simulate the active site of arginase is built starting from the 1.7 A X-ray structure of rat liver arginase complexed with the inhibitor 2(S)-amino-6-boronohexanoic acid (ABH)
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
P05089
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
ir
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Vigna catjang
-
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Q4VK78
-
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
enzyme is involved in acid resistance and inhibits host nitric oxide production
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
enzyme is involved in net production of ornithine, a precursor of polyamines, glutamate, and proline, enzyme is also involved in regulation of nitric oxide biosynthesis by modulating arginine availability for nitric oxide synthase
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
enzyme is involved in regulating L-arginine bioavailability to NO synthase in human penile corpus cavernosum smooth muscle, and in clitoral corpus cavernosum and vagina, enzyme plays a role in both female and male sexual arousal
-
-
ir
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
enzyme is involved in regulation of nitric oxide biosynthesis by modulating arginine availability for nitric oxide synthase
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
-
arginase competes with nitric oxide synthases for L-arginine as the common substrate
-
-
?
L-arginine + H2O
?
show the reaction diagram
-
-
-
-
-
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Helicobacter pylori 43504
-
enzyme is involved in acid resistance and inhibits host nitric oxide production
-
-
?
L-arginine + H2O
L-ornithine + urea
show the reaction diagram
Mus musculus B6/129
-
-
-
-
?
additional information
?
-
-
enzyme may be involved in cellular proliferation in atherosclerosis, inhibiton of enzyme expression by 17beta-estradiol as mechanism in attenuating atherogenensis
-
-
-
additional information
?
-
-
mitochondrial isoform arginase II negatively regulates NO synthase 1 activity by limiting substrate availability in its microdomain
-
-
-
additional information
?
-
-
presence of arginine pools, which are accessible to NO synthase and enzyme, but not exchangeable
-
-
-
additional information
?
-
-
the wild type enzyme does not hydrolyze 1-amino-4-guanidinobutane (agmatine)
-
-
-
additional information
?
-
-
arginase II is constitutively expressed in the airways of normal mice, whereas arginase I is undetectable in normal airways, while its expression is increased in airways of mice exposed to ovalbumin
-
-
-
additional information
?
-
-
complex regulation of natural killer cell functions by arginine availability
-
-
-
additional information
?
-
P78540
hereditary defects in arginase compromise structure and catalysis, which results in an accumulation of arginine in the blood known as hyperarginemia. Arginase deficiency can also result in the accumulation of nitrogen in the form of ammonia, which results in hyperammonemia
-
-
-
additional information
?
-
Q6TA39
infection of mice with Schistosoma mansoni cercariae elevates arginase activity
-
-
-
additional information
?
-
-
recombinant human arginase I (rhArg-PEG), an arginine-depleting enzyme, can inhibit the growth of arginine-dependent tumors
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
52% of the activity with Mn2+
Ca2+
Vigna catjang
-
35% of the activity with Mn2+
Co2+
-
activating
Co2+
-
activating
Co2+
-
activating
Co2+
-
activating
Co2+
-
activating
Co2+
-
activating
Co2+
Bacillus brevis TT02-8
-
activating
Co2+
-
required; required, activates, best metal cofactor
Co2+
-
activates isozyme II 1.46fold, no activation of isozyme I
Co2+
-
45% of the activity with Mn2+
Co2+
Vigna catjang
-
66% of the activity with Mn2+
Co2+
-
displays remarkable activity in the absence of exogenous metals, although manganese, cobalt, and nickel all improve activity. Enzyme shifts its metal preference from Ni, Co,and Mn (decreasing order) when assayed at pH 6 to Ni, Mn, and Co (decreasing order) at pH 9
Co2+
-
enzyme is optimally active with cobalt at pH 6
Co2+
-
enzyme is selective for Co2+
Co2+
-
the Co2+- and Mn2+-reconstituted enzymes exhibit cooperative mechanism of arginine hydrolysis, and undergo self-association and activation with increasing concentrations. Co2+ ions play a more important role in the local tertiary structure of the protein than Mn2+
Co2+
O25949
metal preference in decreasing order: Co2+, Ni2+, Mn2+. Heat-activation in presence of metal ion is essential for activation of apo-enzyme
Fe
-
cysteine-iron promotes arginase activity
Fe2+
-
slight activation
Fe2+
Vigna catjang
-
52% of the activity with Mn2+
Guanidinium chloride
-
the single mutant R308A changes to a trimeric and kinetically cooperative form, whereas the other enzyme variants are not altered
Magnesium
-
stabilizes the protein. In the absence of Mg2+, a complete loss of secondary structure is observed for certain elements
Manganese
-
the more deeply buried Mn2+ ion A is coordinated by residues His193, Asp216, Asp220 and Asp323. The second metal, Mn2+B is co-ordinated by His218, Asp216, Asp323, Asp325
Mg2+
-
93% of the activity with Mn2+
Mg2+
Vigna catjang
-
61% of the activity with Mn2+
Mn2+
-
activating
Mn2+
-
metalloenzyme binding 4 mol Mn2+ per mol enzyme
Mn2+
-
no effect on rat kidney enzyme
Mn2+
-
activating
Mn2+
Pista pacifica
-
activating
Mn2+
-
activating
Mn2+
-
activating
Mn2+
-
activating
Mn2+
-
activating; binds one Mn atom per subunit
Mn2+
-
activating
Mn2+
-
activating
Mn2+
-
activating
Mn2+
-
activating
Mn2+
-
activating
Mn2+
Bacillus brevis TT02-8
-
activating
Mn2+
-
activates, role of weakly and tightly bound metal ions in wild-type and mutant enzymes, metal content, overview
Mn2+
-
manganese-metalloenzyme, binuclear cluster, binding structure
Mn2+
-
15-20% of the activity with Co2+; activates slightly, 14.6% of the activity with Co2+
Mn2+
-
dependent on, manganese-metalloenzyme, wild-type enzyme contains 1.97 mol Mn2+ per mol of subunit, mutants R308A and R308E contain 2.1 mol, and mutant R308K 1.25 mol per mol of subunit
Mn2+
-
dependent on, manganese-metalloenzyme, activates isozyme I, slightly, and isozyme II
Mn2+
-
required for catalysis, enhances lectin function of enzyme
Mn2+
-
activation. after dialysis with EDTA, wild-type and mutant H145N contain 1.1 and 1.3 Mn2+ per subunit, resp., and are hlaf-.active. Mutant H120N contains less than 0.1 Mn2+ per subunit and is inactive
Mn2+
-
maximal activity at 2.0 mM
Mn2+
Vigna catjang
-
maximal activity at 0.6 mM
Mn2+
-
3fold increase in Vmax-value in presence of 0.1 mM Mn2+
Mn2+
-
exogenous addition of Mn2+ results in increased sensitivity to inhibitor sodium fluoride
Mn2+
P05089
binuclear cluster
Mn2+
-
maximum activity at 0.1 mM, presence of Mn2+ results in increase in Vmax, and a higher sensitivity to product and L-lysine inhibition, with no change in KM-value for L-arginine
Mn2+
-
manganese metalloenzyme, each monomer contains two manganese ions
Mn2+
-
essentiell for activity
Mn2+
-
full activation after preincubation for 20 min at 55C with 2 mM Mn2+
Mn2+
Vigna catjang
-
full activation after preincubation for 8 min at 35C with 0.6 mM Mn2+
Mn2+
-
a manganese wash at room temperature is the best condition to purify active enzyme, activity in the presence of 10 mM Mn2+ is at least 15fold higher than in the absence of Mn2+
Mn2+
-
increase in enzyme activity by incubation with 5 mM Mn2+ for 10 min at 60C
Mn2+
-
binuclear manganese metalloenzyme
Mn2+
-
displays remarkable activity in the absence of exogenous metals, although manganese, cobalt, and nickel all improve activity. Enzyme shifts its metal preference from Ni, Co,and Mn (decreasing order) when assayed at pH 6 to Ni, Mn, and Co (decreasing order) at pH 9
Mn2+
-
manganese metalloenzyme; manganese metalloenzyme
Mn2+
-
manganese metalloenzyme, Mn2+-Mn2+ cluster in the active site of each monomer
Mn2+
-
arginase is a better biological catalyst for arginine hydrolysis when both cations are retained and a hydroxide ion is present in the active site bridging the two Mn metal centers
Mn2+
Q6TA39
-
Mn2+
-
the Co2+- and Mn2+-reconstituted enzymes exhibit cooperative mechanism of arginine hydrolysis, and undergo self-association and activation with increasing concentrations. Co2+ ions play a more important role in the local tertiary structure of the protein than Mn2+
Ni2+
-
activation
Ni2+
Bacillus brevis TT02-8
-
activation
Ni2+
-
6-30% of the activity with Co2+; activates slightly, 6.1% of the activity with Co2+
Ni2+
-
51% of the activity with Mn2+
Ni2+
Vigna catjang
-
55% of the activity with Mn2+
Ni2+
-
optimal arginase activity occurrs with nickel at an alkaline pH
Ni2+
O25949
metal preference in decreasing order: Co2+, Ni2+, Mn2+. Heat-activation in presence of metal ion is essential for activation of apo-enzyme
Zn2+
Vigna catjang
-
38% of the activity with Mn2+
Mn2+
O25949
metal preference in decreasing order: Co2+, Ni2+, Mn2+. Heat-activation in presence of metal ion is essential for activation of apo-enzyme
additional information
-
metalloenzyme, a metal ion is absolutely required for activity, no activation with Zn2+, Cu2+, Fe2+, Ca2+, and Mg2+
additional information
-
isozymes are not affected by Mg2+ and Ca2+
additional information
-
no activity with Fe2+, Zn2+
additional information
-
Fe2+, Ca2+, Mg2+, Zn2+, Cu2+ have no effect on enzyme activity
additional information
-
pairwise saturation mutagenesis of the first- and second-shell metal ligands in human arginase I shows that several metal binding ligands are actually quite tolerant to amino acid substitutions. The strict conservation of the second-shell metal binding residues in eukaryotic arginases does not reflect kinetic optimization of the enzyme during the course of evolution
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(-)-epicatechin
-
(-)-epicatechin leads to a decreased arginase-2 mRNA expression after 24 h of incubation, in contrast a weak basal arginase-1 mRNA expression is not affected
(2S)-2-amino-3-(2-amino-1H-imidazol-5-yl)propanoic acid
-
2-aminoimidazole amino acid inhibitor in which the 2-aminoimidazole moiety serves as a guanidine mimetic
(2S)-2-amino-3-(2-amino-1H-imidazol-5-yl)propanoic acid
-
2-aminoimidazole amino acid inhibitor in which the 2-aminoimidazole moiety serves as a guanidine mimetic, significantly attenuates airways hyperresponsiveness in a murine model of allergic airways inflammation
(2S)-2-amino-5-(1H-imidazol-2-ylamino)pentanoic acid
-
2-aminoimidazole amino acid inhibitor in which the 2-aminoimidazole moiety serves as a guanidine mimetic
(2S,5E)-2-amino-7-oxohept-5-enoic acid
-
-
(S)-(2-boronoethyl)-L-cysteine
-
boronic acid-based transition state analogue, classical competitive inhibition at pH 7.5, slow-binding inhibition at pH 9.5
(S)-2-amino-7-oxoheptanoic acid
-
;
(S)-2-amino-7-oxoheptanoic acid
-
-
2(S)-amino-6-boronohexanoic acid
-
boronic acid-based transition state analogue, classical competitive inhibition at pH 7.5, slow-binding inhibition at pH 9.5
2(S)-amino-6-boronohexanoic acid
-
transition state analogue inhibitor
2(S)-amino-6-boronohexanoic acid
-
transition state analogue inhibitor, effect on female and male hemodynamics, overview
2(S)-amino-6-boronohexanoic acid
P05089
Kd-value 5 nM, complete inhibition of enzyme in cytoplasmic extracts of myeloid suppressor cells by 0.05 mM
2(S)-amino-6-boronohexanoic acid
-
0.005 mM, selective arginase inhibitor
2(S)-amino-6-boronohexanoic acid
-
-
2(S)-amino-6-boronohexanoic acid
-
-
2(S)-amino-6-boronohexanoic acid
-
-
2-(1H-indol-3-yl)ethanol
-
-
2-(S)-amino-5-(2-aminoimidazol-1-yl)pentanoic acid
-
2-aminoimidazole amino acid inhibitor in which the 2-aminoimidazole moiety serves as a guanidine mimetic
2-(S)-amino-6-boronohexanoic acid
-
-
2-amino-6-boronohexanoic acid
-
-
2-mercaptoethanol
-
-
2-mercaptoethanol
-
50% inhibition at 0.8 mM
2-mercaptoethanol
O25949
-
2-mercaptopropionate
Q5UNS1, Q5UNS2
5 mM, isoform LeARG1, 38% residual activity, LeARG2, 38% residual activity; 5 mM, isoform LeARG1, 38% residual activity, LeARG2, 38% residual activity
2-oxoarginine
-
-
3-Mercaptopropionate
Q5UNS1, Q5UNS2
5 mM, isoform LeARG1, 24% residual activity, LeARG2, 26% residual activity; 5 mM, isoform LeARG1, 24% residual activity, LeARG2, 26% residual activity
5-hydroxy-L-tryptophan
-
-
5-hydroxytryptamine
-
-
acetyl hydroxamate
-
-
-
adenosine
-
-
Ag+
-
-
agmatine
-
-
Al3+
-
no inhibition of isozyme I, 33% inhibition of isozyme II
Ba2+
-
80% residual activity at 1.5 mM
blasticidin S
Bacillus brevis TT02-8
-
-
Borate
-
buffer
Borate
-
buffer
Borate
-
noncompetitive
Boric acid
-
-
Ca2+
-
inhibitory to enzymic activity in presence of Mn2+, enhances lectin function of enzyme
Cd2+
-
10% inhibition of isozyme I, 86% inhibition of isozyme II
Cd2+
-
mixed competitive inhibitor. Kidney enzyme is more sensitive to inhibition than liver enzyme. Cd2+ enhances substrate activation of kidney enzyme while still being inhibitory. Cd2+ is also inhibitory to kidney enzyme in presence of Mn2+
Chloroquine
-
inhibits arginase in a dose-dependent manner, and displays a linear competitive inhibition on sickle erythrocyte arginase
citrate
-
buffer
citrulline
-
-
Co2+
-
84% residual activity at 1.5 mM
Creatine
Bacillus brevis TT02-8
-
-
Cu2+
-
56% inhibition of isozyme I, 69% inhibition of isozyme II, non-linear allosteric inhibition for isozymes I and II, inhibition is increased with isozyme I by preincubation with the metal ions, not with isozyme II
cycloheximide
-
inhibits protein synthesis
D-Arginine
-
-
D-tryptophan
-
-
diethyl dicarbonate
-
causes a loss in ability of Mn2+ to reactivate inactive subunits of wild-type and mutant enzyme H141F, effect is reversed by hydroxylamine
diethyl dicarbonate
-
second-order rate constant of 113 per M and s for inactivation process. L-ornithine partially protects, L-ornithine plus borate completely protect
diethylene triamine-nitric oxide
-
50% inhibition at 2 mM
dithiothreitol
-
50% inhibition at 0.025 mM
dithiothreitol
-
enzyme depleted of metal and reconstituted with Co2+, complete loss of activiy. Enzyme reconstitued with Mn2+, 20% loss of activity. Loss of catalytic activity in the wild-type protein with dithiothreitol is due to the interaction with Co2+
dithiothreitol
O25949
-
DL-homocysteine
-
-
DTT
-
50% inhibition at 0.025 mM
edeine B1
Bacillus brevis TT02-8
-
-
EDTA
-
-
EDTA
-
-
EDTA
-
after dialysis against EDTA and assay in the absence of Mn2+, the wild type enzyme exhibits 50% activity
EDTA
-
in contrast with R308A, the monomeric E256Q variant of the human enzyme is totally inactivated by dialysis in the presence of EDTA, leading to the suggestion that the quaternary structure could play a role in the affinity of metal binding to arginase
Fe2+
-
78% residual activity at 1.5 mM
Fe3+
-
12% inhibition of isozyme I, 36% inhibition of isozyme II
flavanol-rich cocoa
-
cocoa flavanols lower arginase-2 mRNA expression and activity
-
fluoride
-
substrate inhibition of liver enzyme at concentration above 4 mM, the kidney enzyme is more sensitive and is inhibited uncompetitively, at narrow L-arginie concentration, at 1 mM, preincubation with F- does not affect the enzymes
gamma-guanidinobutyrate
-
-
gamma-guanidinobutyrate
Bacillus brevis TT02-8
-
-
glutathione
Bacillus brevis TT02-8
-
-
Guanidinium chloride
-
-
Guanidinoacetic acid
-
-
Hg2+
-
-
Hg2+
-
80% inhibition of isozyme I, 96% inhibition of isozyme II, non-linear allosteric inhibition for isozymes I and II, inhibition is increased with isozyme I by preincubation with the metal ions, not with isozyme II
HgCl2
Bacillus brevis TT02-8
-
-
hydrogen peroxide
-
50% inhibition at 0.003 mM
imidazole-3-lactate
-
-
indole-3-L-lactic acid
-
-
indole-propionic acid
-
-
Indolepropionic acid
-
-
Indospicine
-
-
Inosine
-
-
Insulin
-
reduces arginase activity
-
L-2-amino-3-guanidinopropionic acid
-
-
L-argininamide
-
-
L-Argininic acid
-
-
L-Argininic acid
-
-
L-canavanine
-
-
L-canavanine
-
-
L-canavanine
-
-
L-cysteine
-
-
L-cysteine
Q6TA39
strongly blocked SmARG-activity
L-glutamate
-
-
L-histidine
Q6TA39
strongly blocked SmARG-activity
L-homoarginine
-
-
L-homoarginine
-
-
L-homoarginine
-
-
L-isoleucine
-
-
L-isoleucine
-
-
L-isoleucine
-
-
L-isoleucine
Bos taurus, Vigna catjang
-
-
L-leucine
-
-
L-leucine
-
-
L-leucine
-
-
L-leucine
Bos taurus, Vigna catjang
-
-
L-lysine
-
-
L-lysine
-
-
L-lysine
-
-
L-lysine
-
-
L-lysine
Bacillus brevis TT02-8
-
-
L-lysine
Vigna catjang
-
-
L-lysine
-
binds to isoform arginase I with Kd of 13.1 microM
L-methionine
-
-
L-N5-(1-iminoethyl)-ornithine
-
-
L-N6-(1-iminoethyl)-lysine
-
-
L-norvaline
-
blocks arginase activity in Actinobacillus actinomycetemcomitans-lipopolysaccharide-stimulated cells
L-ornithine
-
-
L-ornithine
-
-
L-ornithine
Bacillus brevis Nagano
-
-
L-ornithine
-
-
L-ornithine
-
-
L-ornithine
-
-
L-ornithine
Bacillus brevis TT02-8
-
-
L-ornithine
-
product inhibition
L-ornithine
Bos taurus, Vigna catjang
-
-
L-ornithine
Q6TA39
moderately inhibitory
L-proline
-
-
L-proline
-
-
L-proline
Bos taurus, Vigna catjang
-
-
L-thiocitrulline
-
-
L-tryptophan
-
-
L-tryptophan
-
-
L-valine
-
-
L-valine
Bos taurus, Vigna catjang
-
-
lysine
-
-
Mercaptoacetate
Q5UNS1, Q5UNS2
5 mM, isoform LeARG1, 28% residual activity, LeARG2, 26% residual activity; 5 mM, isoform LeARG1, 28% residual activity, LeARG2, 26% residual activity
N-acetyl-5-hydroxytryptamine
-
-
N-bromosuccinimide
Bacillus brevis TT02-8
-
-
N-hydroxy-nor-L-arginine
-
-
Na2AsO4
-
-
-
Ni2+
-
no inhibition of isozyme I, 11% inhibition of isozyme II
Ni2+
-
83% residual activity at 1.5 mM
NOHA
Q6TA39
-
Nomega-amino-L-arginine
-
-
Nomega-hydroxy-L-arginine
-
competitive, reaction intermediate
Nomega-hydroxy-L-arginine
Q5UNS1, Q5UNS2
0.2 mM, isoform LeARG1, 7% residual activity, LeARG2, 5% residual activity; 0.2 mM, isoform LeARG1, 7% residual activity, LeARG2, 5% residual activity
Nomega-hydroxy-L-arginine
-
-
Nomega-hydroxy-L-arginine
Q4A3J0, Q4A3J1, Q4A3J2, Q4A4U9
-
Nomega-hydroxy-L-arginine
-
-
Nomega-hydroxy-L-arginine
-
i.e. NOHA, binds to isoform arginase I with Kd of 3.6 microM
Nomega-hydroxy-nor-arginine
O25949
-
Nomega-hydroxy-nor-L-arginine
-
competitive, reaction intermediate analogue
Nomega-hydroxy-nor-L-arginine
-
-
Nomega-hydroxy-nor-L-arginine
-
in unstimulated HUVEC cells, dose-dependent reduction of enzyme activity, maximum inhibition at 0.02 mM. In cells stimulated by thrombin with or without extracellular L-arginine, stimulation of NO synthase and NO release, with significant reduction of enzyme activity
Nomega-hydroxy-nor-L-arginine
O08701, P07824
nor-NOHA; nor-NOHA
Nomega-hydroxy-nor-L-arginine
Q6TA39
norNOHA
Nomega-hydroxy-nor-L-arginine
-
i.e. nor-NOHA, binds to isoform arginase I with Kd of 517 nM, surface plasmon resonance, or Kd  of 50 nM, isothermal titration calorimetry
Nomega-Nitro-L-arginine
-
-
Nomega-nitro-L-arginine methyl ester
-
i.e. L-NAME, inhibition of enzyme from liver and colon cancer cells in vitro and in vivo
nor-NOHA
-
competitive inhibitor of both isoforms of arginase
p-hydroxymercuribenzoate
-
-
p-hydroxymercuribenzoate
Bacillus brevis Nagano
-
-
Pb2+
-
74% inhibition of isozyme I, 92% inhibition of isozyme II
PEG-SOD
-
polyethylene glycol, covalently linked to superoxide dismutase. Significantly inhibits the arginase activity induced by cysteine-iron, indicating that oxygen species may be responsible in part for the observed increase in arginase activity
-
Polymyxin B
-
blocks arginase activity in Actinobacillus actinomycetemcomitans-lipopolysaccharide-stimulated cells
S-(2-aminoethyl)isothiourea
-
-
S-(2-boronoethyl)-L-cysteine
-
transition state analogue inhibitor
S-(2-boronoethyl)-L-cysteine
-
inhibition results in in reduced fractional shortening, maximal rate of shortening, and relengthening of myocyte contractions
S-(2-boronoethyl)-L-cysteine
-
i.e. BEC, 50% inhibition at 0.005 mM, pH 7.4, or at 0.020 mM, pH 9.0
S-(2-boronoethyl)-L-cysteine
P05089
Kd-value 270 nM
S-(2-boronoethyl)-L-cysteine
-
inhibition results in augmented Ca2+-dependent NO synthase activity and NO production in isolated myocytes
S-(2-boronoethyl)-L-cysteine
Q61176
BEC; BEC
S-(2-boronoethyl)-L-cysteine
-
-
S-(2-boronoethyl)-L-cysteine
-
-
S-(2-boronoethyl)-L-cysteine
O25949
-
S-(2-boronomethyl)-L-cysteine
-
i.e. BMC, 50% inhibition at 3.8 mM, pH 7.4, or at 7.5 mM, pH 9.0
S-(2-boronomethyl)-L-homocysteine
-
i.e. BMHC, 50% inhibition at 0.35 mM, pH 7.4, or above 1 mM, pH 9.0
S-(3-aminopropyl)isothiourea
-
-
S-methyl-L-thiocitrulline
-
-
S-nitrosoglutathione
-
50% inhibition at 0.050 mM
Sodium fluoride
-
noncompetitive
sodium nitroprusside
-
50% inhibition at 0.005 mM
tryptamine
-
-
Woodward's reagent K
-
complete inactivation, reactivation by 0.5 M hydroxylamine. Reactivated enzyme can be inactivated again
Zn2+
-
-
Zn2+
-
13% inhibition of isozyme I, 75% inhibition of isozyme II
Mg2+
-
64% residual activity at 1.5 mM
additional information
-
ornithine is a poor inhibitor of isozyme type II, isozyme selectivity in binding and substrate, products, and inhibitors
-
additional information
-
isothiourea homologues undergo rapid non-enzymic rearrangement to probably give inhibitory compouds, overview
-
additional information
-
effect of preincubation of the isozymes with metal ions, overview
-
additional information
-
binding to lectins is inhibitory to enzymic activity, which is recovered after desorption of the lectin with alpha-D-galactose
-
additional information
-
ebselen does not inhibit arginase, apocynin does not affect the stability of arginase I mRNA but accelerates the decline of arginase activity when protein synthesis is inhibited by cycloheximide
-
additional information
-
cell treatment with anti-CD14 and anti-toll-like receptor 4 but not anti-toll-like receptor 2 antibody decreases arginase activity in Actinobacillus actinomycetemcomitans-lipopolysaccharide-stimulated cells; DL-norvaline does not block arginase activity in Actinobacillus actinomycetemcomitans-lipopolysaccharide-stimulated cells
-
additional information
-
combined polyethylene glycol, covalently linked to superoxide dismutase with a highly stable PEG-catalase, further decrease of arginase activity is observed; salicylic acid derivatives potently inhibited arginase activity. More significant inhibition of arginase activity in purified arginase-1 than in erythrocyte hemolysate, possibly due to the presence of increased extraneous macromolecular interactions in cell hemolysate than in purified enzyme
-
additional information
-
arginase activity functionally inhibits nitric oxide synthase by depleting the substrate pool of L-arginine, and nitric oxide synthase activity potentially inhibits arginase by generating and releasing small amounts of the intermediate N-hydroxy-L-arginine, a competitive inhibitor of arginase, and also by generating nitric oxide itself, which can nitrosylate cysteine residues of human arginase I to modulate its activity; arginase activity functionally inhibits nitric oxide synthase by depleting the substrate pool of L-arginine, and nitric oxide synthase activity potentially inhibits arginase by generating and releasing small amounts of the intermediate N-hydroxy-L-arginine, a competitive inhibitor of arginase, and also by generating nitric oxide itself, which can nitrosylate cysteine residues of human arginase I to modulate its activity
-
additional information
Q6TA39
L-lysine and diaminopimelic acid failed to block SmARG activity
-
additional information
-
testing consequences of inhibiting arginase activity in vivo with NO production, lung inflammation, and lung function in both C57BL/6 and NOS2 knockout mice undergoing ovalbumin-induced airway inflammation, a mouse model of asthma
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cysteine
-
effect of cysteine on arginase activity, effect of increasing concentrations of cysteine alone or in combination with iron (II) sulfate on the enhancement of arginase activity in human sickle erythrocytes or purified arginase-1 from Bos taurus liver
dexamethasone
-
augments arginase activity in Actinobacillus actinomycetemcomitans-lipopolysaccharide-stimulated cells
FeSO4
-
effect of cysteine on arginase activity, effect of increasing concentrations of cysteine alone or in combination with iron (II) sulfate on the enhancement of arginase activity in human sickle erythrocytes or purified arginase-1 from Bos taurus liver
hydralazine
-
treatment with 20 mg/kg/day hydralazine for 5 weeks causes increased arginase activity in hypertensive rats
IL-4
-
interleukin IL-4, up to 16-fold stimulation of enzyme activity in RAW-264.7 cell, in combinantion with rolipram additional activation. No stimulation of enzyme in alveolar macrophages by IL-4 alone, but increase of stimulation by forskolin and 3-isobutyl-1-methylxanthine, IBMX, in presence of IL-4
-
interleukin-4
-
augments arginase activity in Actinobacillus actinomycetemcomitans-lipopolysaccharide-stimulated cells
-
L-arginine
-
strong substrate activation of the kidney enzyme at concentrations above 4 mM
lipopolysaccharide
-
0.001 mg/ml cause a 2fold increase in arginase activity and a marked increase in mRNA encoding arginase I
lipopolysaccharide
-
lipopolysaccharide from Actinobacillus actinomycetemcomitans or Escherichia coli
putrescine
-
activating
TGF-beta
-
transforming growth factor, up to 5-fold stimulation, further stimulation in combination with rolipram
-
Thrombin
-
up to 2fold stimulation, dose- and time-dependent
-
Thrombin
-
endothelial cell exposition to 10 U/ml thrombin for 4 h leads to 1.6fold increased arginase activity
-
thrombin receptor antagonist peptide
-
endothelial cell exposition to 10 U/ml thrombin receptor antagonist peptide for 4 h leads to increased arginase activity
-
Trx1
-
thioredoxin Trx1, stimulation by acting as a chaperone
-
low-density lipoprotein
-
ArgI expression is potently induced by both oxidized and acetylated low-density lipoprotein in macrophages, this effect is mediated by peroxisome proliferator-activated receptors
-
additional information
-
activation at 50-55C in presence of Co2+
-
additional information
-
rolipram increases stimulation by interleukin IL-4 and transforming growth factor beta
-
additional information
-
fibrin has no effect on arginase activity
-
additional information
-
interferon-gamma does not augment arginase activity in Actinobacillus actinomycetemcomitans lipopolysaccharide-stimulated cells
-
additional information
-
treatment with methyl jasmonate. ARGAH1 expression is lower in argah1-1 mutants compared to either wild-type or argah2-1 plants and does not increase in any genotype following methyl jasmonate treatment
-
additional information
-
expression of arginase I strongly correlated with the presence of lung inflammation, as quantified by differential cell counts in lung lavage, suggesting that most, or all, of the arginase I in lungs of mice exposed to ovalbumin is present in the inflammatory cells rather than in the airway epithelium
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.6
1-nitro-3-guanidinobenzene
-
pH 9.0
0.01
4-guanidino-2-nitrophenylacetic acid
-
pH 9.0
0.007
4-guanidino-3-nitrobenzoic acid
-
pH 9.0
2.5
agmatine
-
37C, pH 9.0, mutant N149D
0.69
L-Arg
Bacillus brevis TT02-8
-
-
2.05
L-Arg
-
membrane bound form
3.4
L-Arg
-
-
8.3
L-Arg
-
-
12.8
L-Arg
Bacillus brevis Nagano
-
-
13.5
L-Arg
-
-
15.4
L-Arg
-
-
45
L-Arg
-
-
50
L-Arg
Glycine hispida
-
-
83
L-Arg
-
-
130
L-Arg
-
membrane bound form
0.02
L-arginine
P05089
pH 9.5
0.08
L-arginine
P05089
pH 8.5
0.08
L-arginine
-
mutant S230G, activated by Co2+, pH 7.4, 37C
0.15
L-arginine
-
mutant D181E/S230A, activated by Co2+, pH 7.4, 37C; mutant S230C, activated by Co2+, pH 7.4, 37C; mutant S230D, activated by Co2+, pH 7.4, 37C
0.16
L-arginine
-
mutant S230T, activated by Co2+, pH 7.4, 37C
0.19
L-arginine
-
mutant D181S/S230G, activated by Co2+, pH 7.4, 37C
0.21
L-arginine
-
mutant D181N/S230G, activated by Co2+, pH 7.4, 37C
0.27
L-arginine
-
mutant D181E, activated by Co2+, pH 7.4, 37C
0.28
L-arginine
-
mutant D181S, activated by Co2+, pH 7.4, 37C
0.3
L-arginine
-
wild-type enzyme, pH 9.5
0.3
L-arginine
-
mutant D181N, activated by Co2+, pH 7.4, 37C
0.8
L-arginine
-
mutant S230G, activated by Mn2+, pH 7.4, 37C
1
L-arginine
-
wild type
1
L-arginine
-
-
1.07
L-arginine
-
wild-type enzyme, pH 9.0
1.4
L-arginine
-
pH 9.0
1.4
L-arginine
-
37C, pH 9.0, wild-type
1.5
L-arginine
-
37C, pH 9.0, mutant H145N
1.5
L-arginine
-
wild type enzyme, at 37C
1.5
L-arginine
-
wild-type, pH 9.5
1.5
L-arginine
-
wild type
1.6
L-arginine
-
37C, pH 9.0, mutant H120N
1.81
L-arginine
-
at pH 6.8 and 37C
1.9
L-arginine
-
native rhArg1
2
L-arginine
-
pH 9.2, 37C
2.08
L-arginine
-
at pH 6.8 and 37C
2.1
L-arginine
-
mutant S230C, activated by Mn2+, pH 7.4, 37C
2.4
L-arginine
-
truncated mutant enzyme, pH 9.5
2.5
L-arginine
-
mutant R308A, pH 9.0
2.5
L-arginine
-
T135S mutant, KM increases 2.5fold relatively to values measured for the wild-type enzyme
2.6
L-arginine
-
mutant R308E, pH 9.0
2.7
L-arginine
-
mutant R308K, pH 9.0
2.8
L-arginine
-
mutant D181N/S230G, activated by Mn2+, pH 7.4, 37C
2.9
L-arginine
-
Km of pegylated rhArg1 (rhArg1-peg5,000 mw)
3
L-arginine
-
mutant D181N, activated by Mn2+, pH 7.4, 37C
3.1
L-arginine
-
mutant S89G, Mn2+-activated, pH 5.0, 37C, Hill coefficient 2.1
3.3
L-arginine
-
mutant dN-PFA, pH 8.5, 37C
3.7
L-arginine
-
monomeric E256Q variant, pH 9.5
4
L-arginine
-
mutant dN-PFA-L2S, pH 8.0, 37C; mutant dN-PFA, pH 8.0, 37C
4.4
L-arginine
-
mutant H91A, Co2+-activated, pH 5.0, 37C, Hill coefficient 2.3
4.8
L-arginine
-
about pH 7.0
4.98
L-arginine
-
pH 9.4, 37C, presence of 0.1 mM Mn2+
5
L-arginine
-
mutant C73A, pH 7.2, 37C
5.14
L-arginine
-
pH 9.4, 37C
5.2
L-arginine
-
mutant A92S, Mn2+-activated, pH 5.0, 37C, Hill coefficient 1.6
5.9
L-arginine
-
mutant A92S, Co2+-activated, pH 5.0, 37C, Hill coefficient 1.9; mutant S89G, Co2+-activated, pH 5.0, 37C, Hill coefficient 2.2
6
L-arginine
-
mutant C66A, pH 7.2, 37C
6.2
L-arginine
-
wild-type, pH 7.2, 37C
6.3
L-arginine
-
mutant S88G, Co2+-activated, pH 5.0, 37C, Hill coefficient 2.0
6.4
L-arginine
-
mutant E90A, Co2+-activated, pH 5.0, 37C, Hill coefficient 1.7
6.7
L-arginine
-
pH 5.0, 37C, Mn2+-activited enzyme, K0.5 value, Hill-coefficient 1.6
6.7
L-arginine
-
mutant S88G/A92S, Co2+-activated, pH 5.0, 37C, Hill coefficient 2.0; wild-type, Mn2+-activated, pH 5.0, 37C, Hill coefficient 1.6
7.6
L-arginine
-
at pH 8.5, in H2O buffer
7.7
L-arginine
-
at pH 8.5, in D2O buffer
8.4
L-arginine
-
pH 5.0, 37C, Co2+-activited enzyme, K0.5 value, Hill-coefficient 2.1
8.4
L-arginine
-
wild-type, Co2+-activated, pH 5.0, 37C, Hill coefficient 2.1
8.7
L-arginine
-
mutant S88G, Mn2+-activated, pH 5.0, 37C, Hill coefficient 2.4
9.2
L-arginine
-
mutant S88G/A92S, Mn2+-activated, pH 5.0, 37C, Hill coefficient 2.2
10
L-arginine
-
mutant dN-PFA-H381A, pH 8.0, 37C
12
L-arginine
-
mutant dN-PFA-C6H, pH 8.0, 37C
13
L-arginine
-
T135A mutant, KM is increased 13fold relatively to values measured for the wild-type enzyme
13
L-arginine
-
wild-type, pH 8.0, temperature not specified in the publication
13.3
L-arginine
-
mutant enzyme N130D, at 37C
13.9
L-arginine
-
D183A mutant
17
L-arginine
-
-
17
L-arginine
Q6TA39
pH 10, 37C
19.3
L-arginine
-
N130F mutant
20
L-arginine
-
mutant dN-PFA-L8, pH 8.0, 37C
21.4
L-arginine
-
N130Y mutant
21.5
L-arginine
-
native enzyme
21.8
L-arginine
-
pH 7.1, 37C; pH 7.1, 37C, recombinant enzyme
21.8
L-arginine
-
pH 9.4, 37C
23.9
L-arginine
-
native enzyme
25
L-arginine
-
mutant dN-PFA, pH 7.4, 37C
40
L-arginine
-
D183N mutant
42
L-arginine
Vigna catjang
-
pH 10.0, 37C
45
L-arginine
-
mutant R404A, pH 8.0, temperature not specified in the publication
50
L-arginine
-
N130A mutant
136
L-arginine
-
D183A mutant
146
L-arginine
-
mutant E295R, pH 8.0, temperature not specified in the publication
22.2
L-canavanine
Bacillus brevis TT02-8
-
-
4
S-(4-aminobutyl)isothiourea
-
pH 9.0
2.1
thioguanidino-valeric acid
-
pH 9.0
0.5
L-thioarginine
-
pH 9.0
additional information
additional information
-
-
-
additional information
additional information
Pista pacifica
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
additional information
additional information
-
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0015
1-nitro-3-guanidinobenzene
-
pH 9.0
0.09
4-guanidino-2-nitrophenylacetic acid
-
pH 9.0
0.058
4-guanidino-3-nitrobenzoic acid
-
pH 9.0
2200
L-Arg
-
-
0.013
L-arginine
-
mutant E90A, Co2+-activated, pH 5.0, 37C; mutant H91A, Co2+-activated, pH 5.0, 37C
0.04
L-arginine
-
mutant S89G, Mn2+-activated, pH 5.0, 37C
0.067
L-arginine
-
pH 5.0, 37C, Mn2+-activited enzyme
0.067
L-arginine
-
wild-type, Mn2+-activated, pH 5.0, 37C
0.12
L-arginine
-
mutant S89G, Co2+-activated, pH 5.0, 37C
0.27
L-arginine
-
mutant S88G, Mn2+-activated, pH 5.0, 37C
0.28
L-arginine
-
pH 5.0, 37C, Co2+-activited enzyme
0.28
L-arginine
-
mutant S88G/A92S, Mn2+-activated, pH 5.0, 37C; wild-type, Co2+-activated, pH 5.0, 37C
0.37
L-arginine
-
mutant C66A, pH 7.2, 37C
0.52
L-arginine
-
wild-type, pH 7.2, 37C
0.53
L-arginine
-
mutant C73A, pH 7.2, 37C
0.84
L-arginine
-
mutant A92S, Mn2+-activated, pH 5.0, 37C
0.92
L-arginine
-
mutant A92S, Co2+-activated, pH 5.0, 37C
1
L-arginine
-
mutant E295A, pH 8.0, temperature not specified in the publication
1.01
L-arginine
-
mutant S88G, Co2+-activated, pH 5.0, 37C
1.3
L-arginine
-
mutant E295A/R404A, pH 8.0, temperature not specified in the publication
1.37
L-arginine
-
mutant S88G/A92S, Co2+-activated, pH 5.0, 37C
2 - 8
L-arginine
-
mutant dN-PFA-H381A, pH 8.0, 37C
4.8
L-arginine
-
N130F mutant
6.7
L-arginine
-
mutant E295R, pH 8.0, temperature not specified in the publication
11.4
L-arginine
-
mutant R404A, pH 8.0, temperature not specified in the publication
14.7
L-arginine
-
D183A mutant
17
L-arginine
-
N130Y mutant
24.8
L-arginine
-
wild-type, pH 8.0, temperature not specified in the publication
33
L-arginine
-
mutant enzyme N130D, at 37C
68
L-arginine
-
D183A mutant
72
L-arginine
-
mutant R308K, pH 9.0
76
L-arginine
-
mutant dN-PFA-C6H, pH 8.0, 37C
77
L-arginine
-
mutant dN-PFA, pH 7.4, 37C
84
L-arginine
-
mutant R308A, pH 9.0
89
L-arginine
-
mutant R308E, pH 9.0
131
L-arginine
-
37C, pH 9.0, mutant H120N
140
L-arginine
-
mutant S230D, activated by Co2+, pH 7.4, 37C
167
L-arginine
-
D183N mutant
180
L-arginine
-
monomeric E256Q variant, pH 9.5
180
L-arginine
-
mutant D181S/S230G, activated by Co2+, pH 7.4, 37C
190
L-arginine
-
wild type enzyme, at 37C
190
L-arginine
-
wild-type, pH 9.5
190
L-arginine
-
wild type
200
L-arginine
-
mutant S230G, activated by Co2+, pH 7.4, 37C
203
L-arginine
-
truncated mutant enzyme, pH 9.5
220
L-arginine
-
wild-type enzyme, pH 9.0
220
L-arginine
-
N130A mutant
220
L-arginine
-
mutant D181E/S230A, activated by Co2+, pH 7.4, 37C
231
L-arginine
-
wild-type enzyme, pH 9.5
238
L-arginine
-
37C, pH 9.0, mutant H145N
247
L-arginine
-
mutant D181N/S230G, activated by Co2+, pH 7.4, 37C
249
L-arginine
-
37C, pH 9.0, wild-type
250
L-arginine
-
pH 9.0
260
L-arginine
-
T135A mutant, is reduced 26% relative to values measured for the wild-type enzyme
266
L-arginine
-
mutant S230G, activated by Mn2+, pH 7.4, 37C
285
L-arginine
-
mutant S230C, activated by Mn2+, pH 7.4, 37C
315
L-arginine
-
mutant S230T, activated by Co2+, pH 7.4, 37C
320
L-arginine
-
mutant dN-PFA, pH 8.0, 37C
327
L-arginine
-
mutant S230C, activated by Co2+, pH 7.4, 37C
344
L-arginine
-
mutant D181E, activated by Co2+, pH 7.4, 37C
350
L-arginine
-
T135S mutant, kcat is unchanged relatively to values measured for the wild-type enzyme; wild type
360
L-arginine
-
mutant D181N, activated by Mn2+, pH 7.4, 37C
387
L-arginine
-
mutant D181N, activated by Co2+, pH 7.4, 37C
388
L-arginine
-
mutant D181S, activated by Co2+, pH 7.4, 37C
440
L-arginine
-
mutant dN-PFA, pH 8.5, 37C
517
L-arginine
-
mutant D181N/S230G, activated by Mn2+, pH 7.4, 37C
537
L-arginine
Q6TA39
pH 10, 37C
1132
L-arginine
-
pH 9.4, 37C
300
L-thioarginine
-
pH 9.0
3.33
S-(4-aminobutyl)isothiourea
-
pH 9.0
0.013
thioguanidino-valeric acid
-
pH 9.0
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.03
L-arginine
-
mutant E295R, pH 8.0, temperature not specified in the publication
123
0.062
L-arginine
-
mutant C66A, pH 7.2, 37C
123
0.084
L-arginine
-
wild-type, pH 7.2, 37C
123
0.11
L-arginine
-
mutant C73A, pH 7.2, 37C
123
0.25
L-arginine
-
mutant R404A, pH 8.0, temperature not specified in the publication
123
1.9
L-arginine
-
wild-type, pH 8.0, temperature not specified in the publication
123
2.7
L-arginine
-
mutant dN-PFA-H381A, pH 8.0, 37C
123
2.9
L-arginine
-
mutant dN-PFA-C6H, pH 8.0, 37C
123
3
L-arginine
-
mutant dN-PFA, pH 7.4, 37C
123
80
L-arginine
-
mutant dN-PFA, pH 8.0, 37C
123
120
L-arginine
-
mutant D181N, activated by Mn2+, pH 7.4, 37C
123
133
L-arginine
-
mutant dN-PFA, pH 8.5, 37C
123
136
L-arginine
-
mutant S230C, activated by Mn2+, pH 7.4, 37C
123
185
L-arginine
-
mutant D181N/S230G, activated by Mn2+, pH 7.4, 37C
123
330
L-arginine
-
mutant S230G, activated by Mn2+, pH 7.4, 37C
123
930
L-arginine
-
mutant S230D, activated by Co2+, pH 7.4, 37C
123
950
L-arginine
-
mutant D181S/S230G, activated by Co2+, pH 7.4, 37C
123
1180
L-arginine
-
mutant D181N/S230G, activated by Co2+, pH 7.4, 37C
123
1270
L-arginine
-
mutant D181E, activated by Co2+, pH 7.4, 37C
123
1290
L-arginine
-
mutant D181N, activated by Co2+, pH 7.4, 37C
123
1390
L-arginine
-
mutant D181S, activated by Co2+, pH 7.4, 37C
123
1470
L-arginine
-
mutant D181E/S230A, activated by Co2+, pH 7.4, 37C
123
1970
L-arginine
-
mutant S230T, activated by Co2+, pH 7.4, 37C
123
2180
L-arginine
-
mutant S230C, activated by Co2+, pH 7.4, 37C
123
2600
L-arginine
-
mutant S230G, activated by Co2+, pH 7.4, 37C
123
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.3
(2S)-2-amino-3-(2-amino-1H-imidazol-5-yl)propanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.5
(2S)-2-amino-5-(1H-imidazol-2-ylamino)pentanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.36
(2S,5E)-2-amino-7-oxohept-5-enoic acid
-
pH 9.5
0.00003
(S)-(2-boronoethyl)-L-cysteine
-
pH 9.5, 22C
0.00031
(S)-(2-boronoethyl)-L-cysteine
-
pH 7.5, 22C
0.06
(S)-2-amino-7-oxoheptanoic acid
-
pH 9.5
0.06
(S)-2-amino-7-oxoheptanoic acid
-
-
0.0000085
2(S)-amino-6-boronohexanoic acid
-
pH 9.5, 22C
0.00025
2(S)-amino-6-boronohexanoic acid
-
pH 7.5, 22C
0.01
2(S)-amino-6-boronohexanoic acid
-
mutant dN-PFA, pH 8.5, 37C
0.011
2(S)-amino-6-boronohexanoic acid
-
mutant dN-PFA, pH 7.4, 37C
0.012
2(S)-amino-6-boronohexanoic acid
-
mutant dN-PFA, pH 8.0, 37C
0.053
2(S)-amino-6-boronohexanoic acid
-
mutant dN-PFA-H381A, pH 8.0, 37C
0.004
2-(S)-amino-5-(2-aminoimidazol-1-yl)pentanoic acid
-
pH not specified in the publication, temperature not specified in the publication
0.00015
2-(S)-amino-6-boronohexanoic acid
-
pH 9.5, 25C, supramolecular tandem assay method
0.3
Borate
-
-
0.023
Chloroquine
-
at pH 6.8 and 37C
0.041
Chloroquine
-
at pH 7.4 and 37C
39
Guanidinium chloride
-
mutant enzyme N130D
56
Guanidinium chloride
-
wild type enzyme
3.1
L-lysine
-
presence of 0.1 mM Mn2+, pH 9.4, 37C
5.6
L-lysine
-
pH 9.4, 37C
0.05
L-ornithine
-
product inhibition constant, Co2+-activated mutant S230G, pH 7.4, 37C
0.09
L-ornithine
-
product inhibition constant, Co2+-activated mutant D181N/S230G, pH 7.4, 37C
0.11
L-ornithine
-
product inhibition constant, Co2+-activated mutant D181N, pH 7.4, 37C
0.7
L-ornithine
-
presence of 0.1 mM Mn2+, pH 9.4, 37C
0.7
L-ornithine
-
product inhibition constant, Mn2+-activated mutant S230G, pH 7.4, 37C
1
L-ornithine
-
wild type enzyme
1
L-ornithine
-
product inhibition constant, Mn2+-activated mutant D181N/S230G, pH 7.4, 37C
1.18
L-ornithine
-
pH 9.4, 37C
1.4
L-ornithine
-
pH 9.5, 37C, liver enzyme
1.9
L-ornithine
Q6TA39
pH 10, 37C
2.4
L-ornithine
-
product inhibition constant, Mn2+-activated mutant D181N, pH 7.4, 37C
7.8
L-ornithine
-
pH 9.5, 37C, enzyme from submandibular gland
7.8
L-ornithine
-
mutant enzyme N130D
0.0016
Nomega-hydroxy-L-arginine
-
pH 7.5, 22C
0.014
Nomega-hydroxy-L-arginine
Q5UNS1, Q5UNS2
pH 9.6, 37C; pH 9.6, 37C
0.05
Nomega-hydroxy-L-arginine
-
pH 9.5, 37C, liver enzyme
0.061
Nomega-hydroxy-L-arginine
-
pH 9.5, 37C, enzyme from submandibular gland
0.000051
Nomega-hydroxy-nor-L-arginine
-
pH 7.5, 22C
0.000125
S-(2-boronoethyl)-L-cysteine
-
T135S mutant
0.0004
S-(2-boronoethyl)-L-cysteine
-
wild type
0.0036
S-(2-boronoethyl)-L-cysteine
-
pH 9.5, 25C, supramolecular tandem assay method
0.0045
S-(2-boronoethyl)-L-cysteine
-
T135A mutant
0.013
S-(2-boronoethyl)-L-cysteine
-
N130A mutant
0.38
Sodium fluoride
-
pH 7.4, 37C, thermokinetic method, presence of 0.167 mM Mn2+
0.51
Sodium fluoride
-
pH 7.4, 37C, thermokinetic method
1.48
Sodium fluoride
-
pH 7.4, 37C, initial rate method, presence of 0.167 mM Mn2+
1.84
Sodium fluoride
-
pH 7.4, 37C, initial rate method
5.5
L-proline
-
-
additional information
additional information
-
estimated Ki for several inhibitors, overview, inhibition kinetics
-
additional information
additional information
-
inhibition kinetics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4.8
2-(1H-indol-3-yl)ethanol
-
in the presence of 0.5 mM MnCl2, at 37C
5.3
2-(1H-indol-3-yl)ethanol
-
in the presence of 0.5 mM MnCl2, at 37C
0.00022
2-(S)-amino-6-boronohexanoic acid
-
pH 9.5, 25C, supramolecular tandem assay method
0.03
2-mercaptoethanol
O25949
pH 7.5, 37C
3.6
5-hydroxy-L-tryptophan
-
in the presence of 0.5 mM MnCl2, at 37C
3.9
5-hydroxy-L-tryptophan
-
in the presence of 0.5 mM MnCl2, at 37C
3.3
5-hydroxytryptamine
-
in the presence of 0.5 mM MnCl2, at 37C
3.6
5-hydroxytryptamine
-
in the presence of 0.5 mM MnCl2, at 37C
0.077
Chloroquine
-
at pH 6.8 and 37C
0.109
Chloroquine
-
at pH 7.4 and 37C
8.4
D-tryptophan
-
in the presence of 0.5 mM MnCl2, at 37C
10
D-tryptophan
-
in the presence of 0.5 mM MnCl2, at 37C
0.01
dithiothreitol
O25949
pH 7.5, 37C
20
imidazole-3-lactate
-
IC50 above 20 mM, in the presence of 0.5 mM MnCl2, at 37C
20
indole
-
IC50 above 20 mM, in the presence of 0.5 mM MnCl2, at 37C
3.4
indole-3-L-lactic acid
-
in the presence of 0.5 mM MnCl2, at 37C
3.6
indole-3-L-lactic acid
-
in the presence of 0.5 mM MnCl2, at 37C
2.8
Indolepropionic acid
-
in the presence of 0.5 mM MnCl2, at 37C
2
L-isoleucine
-
-
70
L-isoleucine
Vigna catjang
-
IC50 above 70 mM
2
L-leucine
-
-
70
L-leucine
Vigna catjang
-
IC50 above 70 mM
2
L-lysine
-
-
70
L-lysine
Vigna catjang
-
IC50 above 70 mM
2
L-ornithine
-
-
70
L-ornithine
Vigna catjang
-
IC50 above 70 mM
10
L-proline
Vigna catjang
-
-
70
L-proline
-
-
7.5
L-tryptophan
-
in the presence of 0.5 mM MnCl2, at 37C
8.4
L-tryptophan
-
in the presence of 0.5 mM MnCl2, at 37C
2
L-valine
-
-
70
L-valine
Vigna catjang
-
IC50 above 70 mM
20
N-acetyl-5-hydroxytryptamine
-
IC50 above 20 mM, in the presence of 0.5 mM MnCl2, at 37C
0.5
Nomega-hydroxy-nor-arginine
O25949
pH 7.5, 37C
0.0037
S-(2-boronoethyl)-L-cysteine
-
pH 9.5, 25C, supramolecular tandem assay method
1
S-(2-boronoethyl)-L-cysteine
O25949
pH 7.5, 37C
3.2
tryptamine
-
in the presence of 0.5 mM MnCl2, at 37C
3.4
tryptamine
-
in the presence of 0.5 mM MnCl2, at 37C
20
tyramine
-
IC50 above 20 mM, in the presence of 0.5 mM MnCl2, at 37C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0007
-
Ehrlich ascites carcinoma cell
0.0008
-
sarcoma
0.0012
-
S180 cell
0.00316
-
kidney of sarcoma-bearing mice
0.003175
-
kidney of normal mice
5.8
-
-
8.7
-
pH 9.5, 37C, enzyme from submandibular gland
20.3
-
pH 9.5, 37C, enzyme from parotid gland
30.8
-
pH 9.5, 37C, enzyme from submandibular gland
33
-
homogenate supernatant, in the presence of 10 mM Mn2+
41.5
-
pH 9.5, 37C, enzyme from sublingual gland
41.8 - 888.5
-
range of activity in cirrhotic liver, 37C, pH not specified in the publication
400
-
at 30C, pH 8.5
400
-
about, 30C, pH 8.5
414
Bacillus brevis Nagano
-
-
562
-
pH 9.5, 37C, enzyme from liver
860.4 - 2300
-
range of activity in healthy liver, 37C, pH not specified in the publication
1140
-
35fold purified recombinant enzyme, in the presence of 10 mM Mn2+
1249
-
-
1600
-
pH 9.5, 37C
2045
Vigna catjang
-
pH 10.0, 37C
4746
Bacillus brevis TT02-8
-
-
91300
-
pH 9.2, 37C
additional information
-
-
additional information
-
-
additional information
Glycine hispida
-
-
additional information
Pista pacifica
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
method for radiochemical detection of arginie to citrulline conversion, to measure NO production in intact aorta, presence of enzyme may confound assay
additional information
-
the purified enzyme shows a specific activity of 36.7 U/mg at 37C
additional information
P05089
lung ARG1 expression and activity is increased in human asthma. Expression of ARG1 is increased 4.4fold in lung tissue homogenates from asthma patients compared with controls; no significant differences in ARG2 protein expression is detected between asthma patients and controls by Western blotting or immunoprecipitation
additional information
-
arginase is up to 1000times more active than Helicobacter pylori arginase
additional information
-
increased arginase activity in various malignancies. In cases of carcinoma of the gallbladder the enzyme activity is significantly higher in comparison with cholecystitis
additional information
-
principle of assay, assay protocol
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6
-
Escherichia coli (pBS-barocF) has optimal arginase activity at both pH 6.0 and 9.0 with nickel, with lower activity in the presence of cobalt or manganese
6.1
-
; recombinant enzyme
6.4
O25949
apo-form of enzyme
7
-
with Co2+ and Ni2+
7
-
assay at
7.4
-
assay at
7.4
-
assay at
7.5
Q5UNS1, Q5UNS2
;
9 - 9.5
-
-
9
-
Escherichia coli (pBS-barocF) has optimal arginase activity at both pH 6.0 and 9.0 with nickel, with lower activity in the presence of cobalt or manganese
9.4
-
-
9.5
-
all mutants are kinetically indistinguishable from the wild-type enzyme at the optimum pH of 9.5. At the more physiological, pH 7.5, hyperbolic kinetics is observed for all the mutants, in contrast with the cooperative behavior exhibited by the wild-type species
10
-
with Mn2+
10
-
with Mn2+
10
Bacillus brevis Nagano
-
-
10
Q6TA39
assay at
10.5
Pista pacifica
-
-
11
Bacillus brevis TT02-8
-
-
additional information
-
-
additional information
-
-
additional information
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3
O25949
no residual activity
5.3 - 8.7
-
about 50% of amximal activity at pH 5.3 and pH 8.7
6.5 - 11
-
-
6.5 - 12.5
-
-
7 - 12
Q5UNS1, Q5UNS2
no activity below or above this range; no activity below or above this range
9
O25949
50% of maximum activity
10
Bos taurus, Vigna catjang
-
-
additional information
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
-
assay at room temperature
35
Vigna catjang
-
-
35
Vigna catjang
-
shows highest activity after 8 min preincubation at 35C
37 - 42
-
-
37
-
assay at
37
Q6TA39
assay at
37
-
assay at
55
-
shows highest activity after 20 min preincubation at 55C
60
Pista pacifica
-
-
additional information
-
assay requires heat activation of enzyme in presence of metal cofactor at 50-55C
additional information
-
enzyme activity assay at room temperature
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 42
-
no reproducible temperature preference within this range
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Capra capra
-
-
Manually annotated by BRENDA team
-
intact aorta
Manually annotated by BRENDA team
-
coronary arteriole
Manually annotated by BRENDA team
-
coronary arteriole, enzyme activity increases twofold with hypertension. Inhibition of enzyme activity by Nomega-hydroxy-nor-L-arginine or incubation with L-arginine partially restores NO release and dilation to adenosine in hypertrophic vessels
Manually annotated by BRENDA team
Vigna catjang
-
-
Manually annotated by BRENDA team
Mus musculus B6/129
-
-
-
Manually annotated by BRENDA team
-
endothelial cells isolated from umbilical veins
Manually annotated by BRENDA team
-
type I, postweaning mammals
Manually annotated by BRENDA team
-
sickle erythrocyte
Manually annotated by BRENDA team
-
carcinoma tissue, increased arginase activity in various malignancies. In the event of carcinoma of the gallbladder the enzyme activity is significantly higher in comparison with cholecystitis
Manually annotated by BRENDA team
-
heart homogenate
Manually annotated by BRENDA team
-
normal and hypertrophied feline myocardium, both isoforms arginase-I and arginase-II in crude myocardial homogenate. Arginase-I is downregulated in left ventricular hypertrophy
Manually annotated by BRENDA team
-
HBsAg-positive HCC, HB-8064, liver cancer cell line
Manually annotated by BRENDA team
-
HBV-negative hepatoblastoma, HB-8065, liver cancer cell line
Manually annotated by BRENDA team
-
24h culture, both enzyme and NOS-2 activity depend strongly on extracellular L-arginine concentrations. Competing for L-arginine influx by addition of L-lysine results in 60-70% inhibition of enzyme. Addition of enzyme inhibitor L-valine to cells leads to 80-90% decrease in enzyme activity and 25% increase in NOS-2 activity
Manually annotated by BRENDA team
P05089, P78540
arginase activity in hepatoma cell is nearly 5fold and 15fold lower than in cirrhotic and normal livers, respectively. The amount of arginase I, as well as the expression of arginase I-mRNA are lower in HCC, in comparison with normal liver, and those of arginase II are significantly higher
Manually annotated by BRENDA team
-
arginase activity in hepatoma cell is nearly 5fold and 15fold lower than in cirrhotic and normal livers, respectively. The amount of arginase I, as well as the expression of arginase I-mRNA are lower in hepatoma cell, in comparison with normal liver, and those of arginase II are significantly higher
Manually annotated by BRENDA team
-
intesintal lumen
Manually annotated by BRENDA team
-
macrophage cell, infection with Mycobacterium bovis strain AS-1 lacking an arginine permease. AS-1 infection enhances enzyme activity in resting J774.1 cells. Intracellular growth of AS-1 is enhanced by inhibition of enzyme and of ornithine decarboxylase using L-norvaline and difluoromethylornithine treatment
Manually annotated by BRENDA team
P05089, P78540
-
Manually annotated by BRENDA team
Q4A3J0, Q4A3J1, Q4A3J2, Q4A4U9
mid kidney, basal enzyme expression
Manually annotated by BRENDA team
-
arginase II
Manually annotated by BRENDA team
Q5UNS1, Q5UNS2
induction of isoform LeARG2 upon wounding and treatment with jasmonic acid
Manually annotated by BRENDA team
-
highest enzymic activity
Manually annotated by BRENDA team
-
highest expression of all organs examined
Manually annotated by BRENDA team
-
arginase I
Manually annotated by BRENDA team
-
developmental changes in arginase expression and activity in the lung
Manually annotated by BRENDA team
-
isolated microdissected airway preparations. Arginase II is constitutively expressed in the airways of normal mice, whereas arginase I is undetectable in normal airways, while its expression is increased in airways of mice exposed to ovalbumin
Manually annotated by BRENDA team
-
alveolar macrophage
Manually annotated by BRENDA team
-
alveolar macrophage
Manually annotated by BRENDA team
-
cultured head-kidney derived macrophages, significant enzyme activity, inhibitable by Nomega-hydroxy-L-arginine and induced by dibutyryl cyclic adenosine
Manually annotated by BRENDA team
Q4A3J0, Q4A3J1, Q4A3J2, Q4A4U9
cultured head-kidney derived macrophages, significant enzyme activity, inhibitable by Nomega-hydroxy-L-arginine, not inducible by dibutyryl cyclic adenosine
Manually annotated by BRENDA team
-
isolated cardiac myocyte shows only isoform arginase-I
Manually annotated by BRENDA team
-
isolated myocyte, isoform arginase II
Manually annotated by BRENDA team
-
significant decrease of enzyme activity during 7th-21st day of gestation, significant increase in enzyme activity at term gestation, day 22. Gestational changes in enzyme activity negatively correlate with those in cyclic GMP production and positively correlate with those in endogenous NO synthase inhibitors and endothelin-1 contents. Enhanced enzyme activity at term gestation may be implicated in increasing myometrial contractions mediated by increase in endothelin-1
Manually annotated by BRENDA team
Mus musculus B6/129
-
-
-
Manually annotated by BRENDA team
-
placental villi, isoform arginase-I is observed only in cytophoblasts, arginase-II in both cytophoblasts and synciotrophoblasts. Both isoforms are expressed in the first trimester and at term, enzyme activity is greater in the first trimester than at term
Manually annotated by BRENDA team
-
for ARGAH1, but not ARGAH2
Manually annotated by BRENDA team
-
arginase II
Manually annotated by BRENDA team
-
submandibular, sublingual, and parotid gland
Manually annotated by BRENDA team
-
submandibular, sublingual, and parotid gland, 3.6-7.3% of the activity in liver. In submandibluar gland, presence of both isoform arginase I and arginase II
Manually annotated by BRENDA team
-
GUS staining of seedlings
Manually annotated by BRENDA team
-
rejection of skin xenografts, but not allografts, is associated with a local high production of Th2 cytokines IL-4 and IL-10, overexpression of enzyme, strongly enhanced enzyme activity and attenuated NO generation in the graft
Manually annotated by BRENDA team
-
of penile corpus cavernosum
Manually annotated by BRENDA team
-
mucosal layer of uterine horn, high enzyme activiy
Manually annotated by BRENDA team
-
mucosal layer of vestibula, high enzyme activiy
Manually annotated by BRENDA team
additional information
-
extrahepatic
Manually annotated by BRENDA team
additional information
-
enzyme found in all organs examined
Manually annotated by BRENDA team
additional information
-
enzyme is present at different levels in all parts of cattle reproductive system
Manually annotated by BRENDA team
additional information
Q5UNS1, Q5UNS2
highest levels of enzyme activity in reproductive tissues
Manually annotated by BRENDA team
additional information
-
rejection of skin xenografts, but not allografts, is associated with a local high production of Th2 cytokines IL-4 and IL-10, overexpression of enzyme, strongly enhanced enzyme activity and attenuated NO generation in the graft
Manually annotated by BRENDA team
additional information
O08701, P07824
arginase II is regulated developmentally, and both expression and activity are maximal during fetal life
Manually annotated by BRENDA team
additional information
-
nonhepatic tissue
Manually annotated by BRENDA team
additional information
-
preparation of all and tissue extract
Manually annotated by BRENDA team
additional information
-
type II in mitochondria-containing extrahepatic cells
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30000
-
mutants R308A and R308E, gel filtration
655995
32000
-
gel filtration, replacement of Arg-308 with alanine, with or without truncation, yielded monomeric species
695868
34000
-
mutant R308K, gel filtration
655995
34740
-
theoretical value for unlabeled arginase I
684687
35000
-
gel filtration, recombinant protein
172126
35510
-
MALDI-TOF-MS
697070
35560
-
calculated
697070
37030
-
perdeuterated protein, estimated from amino acid sequence
684687
38000
-
SDS-PAGE
684344
80000
-
gel filtration
687129
86000
-
SDS-PAGE
687129
94400
-
wild-type enzyme, gel filtration
655995
107000
-
gel filtration
172108
110000
-
gel filtration
172100
115000
-
sedimentation analysis, amino acid analysis
172099
117000
-
gel filtration and sucrose density gradient ultracentrifugation
172121
120000
-
-
172106
120000
-
gel filtration
172107
120000
-
gel filtration
668975
120000
-
SDS-PAGE
686646
126000
-
non-denaturing PAGE
172121
138000
-
sedimentation analysis
172096
138000
Glycine hispida
-
gel filtration
172104
138000
-
gel filtration
172121
143000
Bacillus brevis TT02-8
-
gel filtration
172134
180000
Bacillus brevis Nagano
-
gel filtration
172125
191000
-
gel filtration
172110
210000
Vigna catjang
-
gel filtration
668975
220000
-
gel fitration
172122
240000
-
gradient gel electrophoresis
172122
240000
Q6TA39
gel filtration
698355
245000
-
gel filtration
172117
266000
-
gel filtration
172115
330000
-
gel filtration
172114
additional information
Pista pacifica
-
-
172105
additional information
-
-
172113
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 35000, SDS-PAGE
?
-
x * 43000, SDS-PAGE
?
-
x * 37800-40000, about, His-tagged enzyme, sequence calculation and SDS-PAGE
?
-
x * 37000, SDS-PAGE and calculated
?
-
x * 40000, SDS-PAGE, recombinant enzyme with His-tag
?
-
x * 35511, SDS-PAGE
?
Helicobacter pylori 43504
-
x * 37800-40000, about, His-tagged enzyme, sequence calculation and SDS-PAGE, x * 40000, SDS-PAGE, recombinant enzyme with His-tag
-
dimer
-
x-ray crystallography
dimer
-
monomer and dimer with monomer being the major form, but the dimer is associated with higher catalytic activity, analytical gel filtration. The proportion of dimer decreases with increasing salt concentrations
heterodimer
-
1 * 34000 + 1 * 52000, SDS-PAGE
hexamer
Q6TA39
6 * 40000, SDS-PAGE
hexamer
Bacillus brevis Nagano
-
6 * 32000, SDS-PAGE
hexamer
-
6 * 38300, SDS-PAGE
hexamer
-
6 * 36500, SDS-PAGE
monomer
-
1 * 35000, recombinant protein, SDS-PAGE
monomer
-
1 * 30000-34000, mutant enzymes R308A, R308E, and R308K
monomer
-
replacement of Arg-308 with alanine, with or without truncation, yielded monomeric species
monomer
O25949
apo-form of enzyme, gel fitlration
oligomer
-
x * 35000, SDS-PAGE
oligomer
-
x * 36500, SDS-PAGE
oligomer
Pista pacifica
-
x * 34000, SDS-PAGE
tetramer
-
4 * 31000, SDS-PAGE
tetramer
Vigna catjang
-
4 * 52000, SDS-PAGE
tetramer
-
4 * 30800, sedimentation equilibrium urea
tetramer
-
4 * 37000, gel filtration with previous SDS treatment
tetramer
Bacillus brevis TT02-8
-
4 * 33000, SDS-PAGE
tetramer
Rhodobacter capsulatus E1F1
-
4 * 31000, SDS-PAGE
-
trimer
-
3 * 37000, SDS-PAGE
trimer
-
3 * 35000, SDS-PAGE, wild-type enzyme
trimer
-
primarily, higher order oligomers are also observed
trimer
-
the trimeric state is the active form of the protein, X-ray scattering
trimer
-
trimeric quaternary structure in which each monomer adopts an alpha/betafold consisting of a central parallel eight-stranded beta-sheet flanked on both sides by several alpha-helices
monomer
-
monomer and dimer with monomer being the major form, but the dimer is associated with higher catalytic activity, analytical gel filtration. The proportion of dimer decreases with increasing salt concentrations
additional information
-
-
additional information
-
-
additional information
-
monomer-monomer-interactions are stabilized by a arginine-rich network of intersubunit salt bridges, sulfate counterions, and hydrogen bonds more extensive than that observed in isozyme I
additional information
-
isolated myocyte, enzyme arginase II co-immunoprecipitates with NO synthase 1, but not with NO synthase 3
additional information
-
functional significance of a C-terminal S-shaped motif (residues 304-322) is explored by examining the kinetic properties of the R308A mutant and truncated species terminating in either Arg-308 or Ala-308
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
280 glucose residues, 27 fructose residues, 85 mannose residues per molecule
proteolytic modification
-
enzyme sequence contains a glycosomal targeting signal
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant arginase
-
-
Glycine hispida
-
homology modeling based on Bacillus caldovelox crystal structure. Residues D116, D120, D234, D236 and H91, H118, H133 contribute to catalysis and stability of binuclear metal center of arginase and have an important role in binding and catalytic activity in the active site
-
12-16 mg/ml purified recombinant wild-type enzyme and mutant H141C complexed with substrate L-arginine, reaction intermediate Nomega-hydroxy-L-arginine and analogue Nomega-hydroxy-nor-L-arginine, hanging drop vapour diffusion method, equal columns of protein and precipitant solution containing 50 mM bicine, pH 8.5 at 22C, 12-18% PEG 8000, 5 mM MnCl2, equilibration at 4C over 1 ml precipitant solution as reservoir, pyramidal crystals after 4 weeks, complex preparation by soaking of crystals in 18% PEG 8000, 50 bicine, pH 8.5, 5 mM MnCl2, and 5 mM of Nomega-hydroxy-L-arginine and L-arginine for 6 days, complex formation with analogue Nomega-hydroxy-nor-L-arginine affords equilibration to pH 7.5, X-ray diffraction structure determination and analysis at 2.0-2.9 A resolution
-
7 mg/ml purified fully active, untruncated enzyme complexed with 5 mM inhibitor S-(2-boronoethyl)-L-cysteine in 50 mM bicine, pH 8.5, 0.003 ml mixed with 0.1 ml MnCl2 and 0.003 ml precipitant solution containing 0.1 M Tris-HCl, pH 8.3-8.5, 3 M ammonium sulfate, equilibration over 1 ml reservoir solution containing 0.1 M Tris-HCl, pH 8.3-8.5, 3 M ammonium sulfate, and 20% v/v glycerol, hanging drop vapour diffusion method at 4C, X-ray diffraction structure determination and analysis at 2.7 A resolution
-
D183A and D183N mutants of human arginase I complexed with 2(S)-amino-6-boronohexanoic acid are crystallized by the sitting drop vapor diffusion method at 21C
-
in complex with inhibitors 2(S)-amino-6-boronohexanoic acid or S-(2-boronoethyl)-L-cysteine
P05089
in complex with inhibitors N-hydroxy-L-arginine and nor-N-hydroxy-L-arginine, to 2.04 and 1.55 A resolution, respectively, and in complex with L-lysine, to 1.9 A resolution. Enzyme forms hydrogen bond interactions with inhibitor alpha-carboxylate and alpha-amino groups
-
sitting drop vapour diffusion method with 0.1 M Bis-Tris-HCl (pH 5.5), 10-20% (w/v) PEG-3350
-
homology modelling and molecular dynamics study on the mechanism of metal dependency. When the active site metals are removed, loss of structural integrity is observed reflected by a larger equilibration root mean square deviation for the protein when the active site metal is removed and some loss of secondary structure. An inter-monomer salt-bridge between Glu295 and Arg404 is associated with the metal dependency
-
in complex with the boronic acid inhibitor 2(S)-amino-6-boronohexanoic acid, to 2.15 A resolution. There are two polypeptide insertions unique to malarial arginase, a 74-residue low complexity region contained in loop L2 and an 11-residue segment contained in loop L8. Structural studies indicate that the low-complexity region is largely disordered and is oriented away from the trimer interface, its deletion does not significantly compromise enzyme activity. The loop L8 insertion is located at the trimer interface and makes several intra- and intermolecular interactions important for enzyme function
-
isoform arginase I in complex with inhibitor (S)-2-amino-7-oxoheptanoic acid. Inhibitor aldehyde moiety is hydrated to form the gem-diol, one hydroxyl group bridges the Mn2+ cluster and donates a hydrogen bond to D128, and the second hydroxyl group donates a hydrogen bond to E277
-
recombinant R308K mutant, X-ray diffraction structure determination and analysis at 3.0 A resolution
-
T135A rat arginase I-BEC complex and unliganded N130A rat arginase I are crystallized by the hanging drop vapor diffusion method at 4C
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 9
-
below pH 6.0 and above 9.0 rapid loss of activity
172094
8.5 - 9.5
-
-
172121
9 - 12
-
after 60 min incubation at 50C no loss of activity
172102
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
-20
-
no loss of activity for several months
172121
0 - 4
-
no loss of activity after 12 days
172101
4
-
stable for at least 1 month
172122
50 - 55
-
activation in presence of Co2+
655481
50 - 55
-
activity increased about 10fold following treatment with heat (50-55C, 30 min) at pH 9.0 in the absence of metal versus no heat, in the presence of various metals, heat treatment does not affect arginase activity at either pH 6.0 or 9.0, when compared to samples that are not heat-treated
696954
55
-
no loss of activity after 60 min below 55C
172102
60
-
no loss of activity after 10 min
172101
60
-
stable
668975
60
-
activity drops rapidly above 60C
687129
62
-
melting temperature, mutants C73A and C66A depleted of Co2+
711098
66
-
melting temperature, mutant C73A
711098
67
-
melting temperature, mutant C66A
711098
69
-
melting temperature, wild-type depleted of Co2+
711098
69
-
melting temperature, apo-form of wild-type
719623
71
-
melting temperature, wild-type
711098
71
-
melting temperature, holo-form of wild-type
719623
additional information
-
metal ions protect from heat inactivation
172094
additional information
-
frozen: rapid loss of activity
172101
additional information
-
MnCl2 or L-threonine protect from heat inactivation
172102
additional information
-
-
172107
additional information
-
-
172116
additional information
-
additional information
172127
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
dialysis results in in loss of over 90% activity, highly unstable enzyme
-
recombinant protein, highly unstable
-
perdeuterated human arginase I exhibits catalytic activity essentially identical to that of the unlabeled enzyme
-
unstable at high dilution, ornithine or glycine stabilize
-
at pH 2 or with SDS at pH 10 in absence of Mn2+, inactivation due to dissociation into subunits
-
L-valine, 25 mM, stabilizes during purification
-
additional information
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, His-tagged recombinant protein, 1:2 dilution with 100% glycerol, 4 months, 45-65% loss of activity
-
-20C, purified recombinant enzyme, 1:2 with glycerol, loss of 45-65% activity after 4 months, and of over 90% after 6 months
-
4C, His-tagged recombinant protein, 1:2 dilution with 100% glycerol, 1 week, 90% loss of activity
-
4C, purified recombinant enzyme, 1:2 with glycerol, over 90% loss of activity within 1 week
-
-20C, for at least 3 months
-
4C, aqueous solutions, pH 7
-
-10C or 4C, unstable
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
-
Bacillus brevis TT02-8
-
expressed in Escherichia coli
-
ammonium sulfate precipitation, AH-Sepharose 4B column chromatography, and gel filtration
-
two isoenzymes
-
DEAE-cellulose column chromatography, CM-Sephadex column chromatography, and Bio-Gel P-100 gel filtration
-
-
Glycine hispida
-
recombinant enzyme from Escherichia coli
-
DEAE-cellulose column chromatography
-
expressed in Escherichia coli
-
nickel affinity column chromatography
-
recombinant enzyme to homogeneity
-
recombinant wild-type and mutant enzymes from Escherichia coli
-
recombinant wild-type and truncated mutant enzymes from Escherichia coli BL21(DE3)
-
HiTrap Ni2+-chelating Sepharose column chromatography
-
partially from vaginal tissue
-
recombinant wild-type and mutant enzymes from Escherichia coli
-
-
Vigna catjang
-
ammonium sulfate precipitation, AH-Sepharose 4B column chromatography, and gel filtration
Vigna catjang
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
-
expressed in Escherichia coli
-
-
Q4A3J0, Q4A3J1, Q4A3J2, Q4A4U9
expression in Escherichia coli
-
expression of apo-enzyme in a Mn2+- and Co2+-free minimal medium
O25949
gene rocF, functional expression in Escherichia coli DH5alpha as His-tagged enzyme
-
expressed in Escherichia coli
-
expressed in Escherichia coli and expressed in Bacillus subtilis as a N-terminal 6xHistagged protein
-
expressed in Escherichia coli BL21 (DE3) cells
-
expressed in Escherichia coli strain JM109
-
expression in Escherichia coli
-
expression in Saccharomyces cerevisiae
-
expression of wild-type and mutant enzymes in Escherichia coli
-
expression of wild-type and truncated mutant enzymes in Escherichia coli BL21(DE3)
-
mutants are overexpressed and purified from Escherichia coli BL21(DE3) cells using a pBS(KS) vector
-
expressed in Escherichia coli BL21 cells
-
mutants are overexpressed and purified from Escherichia coli BL21(DE3) cells using a pET29b expression vector
-
overexpression of wild-type and mutant enzymes in Escherichia coli BL21(DE3)
-
expressed in Escherichia coli strain DH5alpha
Q6TA39
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
exposure to ONOO- generator SIN-1 or to H2O2 increases arginase I expression and arginase activity by 35% and 50%, respectively, which is prevented by ROCK inhibitor, Y-27632, PKC inhibitor, G6976 or siRNA to p115-Rho GEF. The oxidative species ONOO- and H2O2 increase arginase activity/expression through PKC-mediated activation of RhoA/Rho kinase pathway
-
arginase AI activity and its mRNA level are significantly decreased in cirrhotic liver
-
both ARG1 and ARG2 are expressed by hormone-sensitive and hormone-refractory prostate cancer cell lines, with the LNCaP cells having the highest arginase activity. In prostate tissue samples, ARG2 is more expressed in normal and non-malignant prostatic tissues compared to tumor tissues. Following androgen stimulation of LNCaP cells with 10 nM R1881, both ARG1 and ARG2 are overexpressed. The regulation of arginase expression following androgen stimulation is dependent on the androgen receptor. Interleukin-8 is also upregulated following androgen stimulation and it directly increases the expression of ARG1 and ARG2 in the absence of androgens
-
arginase AII activity and its mRNA level are significantly raised in cirrhotic liver
-
stimulated by cytokines, inflammatory stimuli, cAMP
-
coinhibitory and costimulatory molecules PD-1 and CTLA-4 on the Gr-1+CD11b+ myeloid-derived suppression cells regulate the activity and expression of arginase I. The blockage and silencing of PD-1, CTLA-4 or both PD-1 and CTLA4 molecules can significantly reduce arginase I activity and expression induced with tumor-associated factor. CD80 deficiency also decreases the arginase I expression and activity
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A92S
-
mutation of A92 to its analogous residues in other arginases individually enhances the catalytic activity
C66A
-
residue involved in disulfide bond. Catalytic turnover and the catalytic efficiency for the mutant proteins similar to the wild-type
C73A
-
residue involved in disulfide bond. Catalytic turnover and the catalytic efficiency for the mutant proteins similar to the wild-type
D116A
-
no detectable activity
E90A
-
residue E90 is important for catalytic activity and plays a crucial role in retaining the metal ion at the active site
E90A/H118A
-
no detectable activity
S88G
-
mutation of Ser88 to its analogous residues in other arginases individually enhances the catalytic activity
S88G/A92S
-
mutation of S88 and A92 to its analogous residues in other arginases individually enhances the catalytic activity
S89G
-
1.5fold decrease in catalytic activity
D181E
-
with Co2+, rate similar to wild-type
D181E/S230A
-
with Co2+, rate similar to wild-type
D181N
-
with Co2+, rate similar to wild-type
D181N/S230G
-
with Co2+, rate similar to wild-type
D181S
-
with Co2+, rate similar to wild-type
D181S/S230G
-
with Co2+, rate similar to wild-type
D183A
-
site-directed mutagenesis. D183A substitution completely abolishes the hydrogen bond with the alpha-amino group of the inhibitor, resulting in 1400fold diminished affinity as well as a diminished occupancy of 0.5 for inhibitor binding in the crystal structure
D183N
-
site-directed mutagenesis. D183N substitution results solely from the altered electrostatics of the interaction with the alpha-amino group of the inhibitor
E256Q
-
In contrast with R308A, the monomeric E256Q variant of the human enzyme is totally inactivated by dialysis in the presence of EDTA, leading to the suggestion that the quaternary structure could play a role in the affinity of metal binding to arginase
H101N
-
60% of wild-type activity, unaltered Km for arginine and Ki for lysine compared to the wild-type enzyme
H120N
-
53% of wild-type activity, no alteration in KM-value
H126N
-
82% of wild-type activity, unaltered Km for arginine and Ki for lysine compared to the wild-type enzyme
H141C
-
site-directed mutagenesis, crystal structure determination with bound substrate and reaction intermediate
H141F
-
activation by Mn2+
H141F
-
mutant enzyme is completely resistant to inactivation by Woodwards reagent K
N130D
-
17% activity compared to the wild type enzyme, the mutant is also active on agmatine, the N130D mutant enzyme is inactive after dialysis against EDTA and assay in the absence of Mn2+
N130Q
-
after dialysis against EDTA and assay in the absence of Mn2+, the wild type-like N130Q mutant enzyme exhibits 50% activity
N149D
-
almost complete loss of activity with L-arginine, gain of activity with agmatine
R308A
-
site-directed mutagenesis, single mutant R308A changed to a trimeric and kinetically cooperative form, with or without truncation
S230C
-
with Co2+, about 2fold increase in rate, compared to wild-type
S230D
-
with Co2+, rate similar to wild-type
S230G
-
with Co2+, 2fold increase in rate, compared to wild-type
E295A
-
96% decrease in activity. Residue is not involved in inter-monomer salt bridge
E295A/R404A
-
95% decrease in activity
R404A
-
54% decrease in activity, lack of trimer association. Residue is not involved in inter-monomer salt bridge
N130A
-
site-directed mutagenesis. The value of KM is increased 50fold, whereas the value of kcat is reduced only 37%, relative to values measured for the wild-type enzyme
N130F
-
site-directed mutagenesis
N130Y
-
site-directed mutagenesis
R308A
-
site-directed mutagenesis, 17% activity compared to the wild-type enzyme, mutant forms monomers instead of trimers like the wild-type enzyme, reduced unfolding temperature compared to the wild-type enzyme
R308E
-
site-directed mutagenesis, 17% activity compared to the wild-type enzyme, mutant forms monomers instead of trimers like the wild-type enzyme, reduced unfolding temperature compared to the wild-type enzyme
R308K
-
site-directed mutagenesis, 13% activity compared to the wild-type enzyme, mutant forms monomers instead of trimers like the wild-type enzyme, reduced unfolding temperature compared to the wild-type enzyme
T135A
-
site-directed mutagenesis, substitution of T135 with Ala destroys hydrogen-bonding potential
T135S
-
site-directed mutagenesis, substitution of T135 with serine conserves hydrogen-bonding potential
additional information
-
disruption of enzyme structural genes ARGAH1 or ARGAH2 accentuates the increases of transcript levels of basic amino acid transporter BAC1 at germination and of BAC2 two days after germination. Early expression of BAC1 and BAC2 is consistent with the delivery of arginine to the mitochondrial enzyme and the export of ornithine
additional information
-
activity is greatly reduced in an argah1-1 null mutant, but not in an argah2-1 null mutant
additional information
-
arginase-negative mutants of Arabidopsis exhibit increased nitric oxide signaling in root development. argah1-1 and argah2-1 arginase-negative mutants. Arginase-negative mutant argah1-1 retains about 85% of total arginase activity. NO accumulation is differentially enhanced in argah1-1 and argah2-1 compared with the wild type
H91A
-
residue E90 is important for catalytic activity and plays a crucial role in retaining the metal ion at the active site
additional information
-
enzyme disruption mutant. Helicobacter pylori extracts and intact Helicobacter pylori of wild-type, but not of enzyme deficient mutant, induce a decreased expression of CD3zeta-chain of the TCR in Jurkat cells and reduce proliferation of freshly isolated human normal T-lymphocytes
H145N
-
95% of wild-type activity, no alteration in KM-value
additional information
-
construction of the truncated mutant DELTAM1-V23/DELTAH331-I354 showing reduced acivity compared to the wild-type enzyme
additional information
-
pairwise saturation mutagenesis of the first- and second-shell metal ligands in human arginase I. Certain second-shell mutations can modulate the binding of both the nucleophilic water/hydroxide molecule and substrate or product ligands, resulting in activity greater than that of the wild-type enzyme. The strict conservation of the second-shell metal binding residues in eukaryotic arginases does not reflect kinetic optimization of the enzyme during the course of evolution
S230T
-
with Co2+, about 1.5fold increase in rate, compared to wild-type
additional information
-
enzyme deletion mutant, parasites express no enzymic activity, lack an intracellular ornithine pool, and are auxotrophic for ornithine or polyamines. Expression of a mutant enzyme lacking the glycosomal targeting sequence leads to an enzyme mislocalized to the cytosol and there restoring the polyamine auxotrophy of the deletion mutant
medicine
-
infection of macrophage cell J774.1 with Mycobacterium bovis strain AS-1 lacking an arginine permease. AS-1 infection enhances enzyme activity in resting J774.1 cells. Intracellular growth of AS-1 is enhanced by inhibition of enzyme and of ornithine decarboxylase using L-norvaline and difluoromethylornithine treatment
additional information
Q61176
OVA/OVA mice, murine models of ovalbumin-induced airway inflammation, OVA/OVA mice, murine models of ovalbumin-induced airway inflammation, ARG1 expression is similar to the sam ples from asthma patients. ARG1 is visibly increased throughout the lungs, and strong-positive staining is observed in infiltrating inflammatory cells, bronchiolar and alveolar macrophages, and the peribronchiolar regions in the OVA/OVA mice
E295R
-
73% decrease in activity
additional information
-
construction of a N-terminal truncation beginning with K22 and bearing an N-terminal His-tag, i.e. dN-PFA, a similar N-terminal truncation with residues N84-D157 of loop L2 deleted, i.e. dN-PFA-L2S, mutant dN-PFA-H381A, and the dN-PFA-L8 chimera in which loop L8 is replaced with the shorter human arginase I sequence, and analysis of kinetic parameters
D183A
-
site-directed mutagenesis. KM is increased 14fold, whereas the value of kcat is reduced 24fold, relative to values measured for the wild-type enzyme
additional information
-
mutation of H141 to study its role in catalysis
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
renaturation of heat- or urea-denatured enzyme by chaperone thioredoxin Trx1 from Helicobacter pylori extracts
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
assay method based on a combination of moderately selective host-guest binding with the specificity of enzymatic transformations which allows the real-time monitoring of enzymatic reactions in a homogeneous solution. The resulting supramolecular tandem assays exploit the dynamic binding of a fluorescent dye with a macrocyclic host in competition with the binding of the substrate and product. The depletion of the substrate allows the fluorescent dye to enter the macrocycle in the course of the enzymatic reaction, which leads to the desired fluorescence response. For arginase, p-sulfonatocalix[4]arene is used as the macrocycle, which displays binding constants of 6400 per M with arginine, 550 per M with ornithine, and 60 000 per M with the selected fluorescent dye 1-aminomethyl-2,3-diazabicyclo[2.2.2]oct-2-ene, the dye shows a weaker fluorescence in its complexed state, which leads to a switch-off fluorescence response in the course of the enzymatic reaction. Assays can be successfully used to probe the inhibition of enzymes
medicine
-
new forms of efficient arginase inhibitors, could be useful as therapeutic regimen in hemoglobinopathies and other related inflammation-mediated diseases
medicine
-
exposure to ONOO- generator SIN-1 or to H2O2 increases arginase I expression and arginase activity by 35% and 50%, respectively, which is prevented by ROCK inhibitor, Y-27632, PKC inhibitor, G6976 or siRNA to p115-Rho GEF. The oxidative species ONOO- and H2O2 increase arginase activity/expression through PKC-mediated activation of RhoA/Rho kinase pathway
medicine
-
enzyme is involved in T-cell function during infection. Helicobacter pylori extracts and intact Helicobacter pylori of wild-type, but not of enzyme deficient mutant, induce a decreased expression of CD3zeta-chain of the TCR in Jurkat cells and reduce proliferation of freshly isolated human normal T-lymphocytes
analysis
-
development of a high-throughput semiquantitative assay system using a colorimetric 96-well plate assay to monitor the formation of urea. The assay has a dynamic range of about 5-300 microM for the ureido product
drug development
-
the application of rhArg-PEG alone or in combination with existing chemotherapeutic drugs may represent a specific and effective therapeutic strategy against human hepatocellular carcinoma
medicine
-
enzyme is a target for inhibitors used in therapeutic treatment of smooth muscle disorders, such as erectile dysfunction
medicine
-
agents that elevate cAMP level significantly enhance induction of enzyme by cytokines. Consequences of increased enzyme expression should be evaluated when phosphodiesterase inhibitors are used for treatment of inflammatory disorders in which IL-4 and/or TGF-beta predominate
medicine
-
patients with cystic fibrosis, before and after 14 days of antibiotic treatment for pulmonary exacerbation. Systemic enzyme levles are significantly increased in cystic fibrosis with exacerbation. Enzyme levels normalize with antibiotic treatment. Plasma L-arginine is reduced before, but not after treatment, L-ornithine, L-proline, and L-glutamic acid are normal before and increased after treatment
medicine
-
plasma arginase activity is significantly elevated in patients with sickle cell disease, with highest activity found in patients with secondary pulmonary hypertension. Arginase activity correlates with the arginine-ornithine ratio, and lower ratios are associated with greater severity of pulmonary hypertension and with mortality. Increased plasma enzyme activity is correlated with increased intravascular hemolytic rate and, to a lesser extent, with markers of inflammation and soluble adhesion molecule levels
medicine
-
targeting vascular arginase as a therapeutic possibility for atherosclerosis. Thrombin enhances enzyme activity via small G-protein RhoA/ROCK in endothelial cells
medicine
-
enzyme serves as a therapeutic target for the treatment of asthma, erectile dysfunction, and atherosclerosis
medicine
-
a significant decrease in arginase activity, dependent of the liver clinical stage, is observed in cirrhotic tissue. Arginase AI activity and its mRNA level are significantly decreased in cirrhotic liver, whereas the activity and expression of arginase AII are concurrently raised, as compared to normal liver
medicine
-
both ARG1 and ARG2 are expressed by hormone-sensitive and hormone-refractory prostate cancer cell lines, with the LNCaP cells having the highest arginase activity. In prostate tissue samples, ARG2 is more expressed in normal and non-malignant prostatic tissues compared to tumor tissues. Following androgen stimulation of LNCaP cells with 10 nM R1881, both ARG1 and ARG2 are overexpressed. The regulation of arginase expression following androgen stimulation is dependent on the androgen receptor. This observation is correlated in vivo in patients by immunohistochemistry. Patients treated by androgen-deprivation therapy prior to surgery have lower ARG2 expression in both nonmalignant and malignant tissues. ARG1 and ARG2 are enzymatically active and their decreased expression by siRNA results in reduced overall arginase activity and L-arginine metabolism. The decreased ARG1 and ARG2 expression also translates with diminished LNCaP cells cell growth and increased peripheral blood mononuclear cell activation following exposure to LNCaP cells conditioned media. Interleukin-8 is also upregulated following androgen stimulation and it directly increases the expression of ARG1 and ARG2 in the absence of androgens
medicine
-
Co2+ substitution of the Mn2+ metal cofactor confers more than 10fold higher catalytic activity and 5fold greater stability. Based on the hypothesis that the Co-ArgI enzyme would decrease tumor burden by systemic elimination of L-arg in a murine model, Co-hArgI was conjugated to 5-kDa PEG to enhance circulation persistence and applied as monotherapy for hepatocellular carcinoma and pancreatic carcinoma in vitro and in vivo murine xenografts. Weekly treatment of 8 mg/kg Co-hArgI-PEG effectively controls human HepG2 and Panc-1 tumor xenografts. Both cell lines underwent apoptosis in vitro with significant increased expression of activated caspase-3 and showed evidence of autophagy in vitro and in vivo
pharmacology
-
enzyme is a target for inhibitor design based on arginine analogues with uncharged, tetrahedral functional groups
analysis
-
specific detection of NO production in intact mouse tissue, inhibition of enzyme by N-hydroxy-nor-L-arginine to avoid disturbances
medicine
-
overexpression of arginase in the penis contributes to erectile dysfunction
medicine
-
arginase gene expression in the lung is linked to asthma both in clinical studies of human patients and in the well-studied mouse model of ovalbumin-induced airway inflammation
medicine
-
bone marrow cell derived arginase I is the predominant source of allergen-induced lung arginase but is not required for allergen-induced inflammation, airway hyperresponsiveness or collagen deposition
medicine
-
coinhibitory and costimulatory molecules PD-1 and CTLA-4 on the Gr-1+CD11b+ myeloid-derived suppression cells regulate the activity and expression of arginase I. The blockage and silencing of PD-1, CTLA-4 or both PD-1 and CTLA4 molecules can significantly reduce arginase I activity and expression induced with tumor-associated factor. Similar results are also observed while their ligands B7-H1 and/or CD80 are blocked or silenced. CD80 deficiency also decreases the arginase I expression and activity. Antibody blockade or silencing of PD-1, CTLA-4 or both reduces the suppressive potential of PD-1+CTLA-4+ myeloid-derived suppression cells. Blockade of PD-1, CTLA-4 or both also slows tumor growth and improves the survival rate of tumor-bearing mice
medicine
Mus musculus B6/129
-
overexpression of arginase in the penis contributes to erectile dysfunction
-
medicine
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oopherectomized animals treated with 0.5% cholesterol-enriched diet. Diet results in increase in plasma lipids, atheromatous lesions as well as expression of enzyme isoforms arginase I and II and an increase in cellular proliferation. Diet plus supplementation of 17beta-estradiol results in a decrease of atheromatous lesions and reduced expression of both enzyme isoforms and inducible NO synthase. Inhibiton of enzyme expression by 17beta-estradiol as mechanism in attenuating atherogenensis
nutrition
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oopherectomized animals treated with 0.5% cholesterol-enriched diet. Diet results in increase in plasma lipids, atheromatous lesions as well as expression of enzyme isoforms arginase I and II and an increase in cellular proliferation. Diet plus supplementation of 17beta-estradiol results in a decrease of atheromatous lesions and reduced expression of both enzyme isoforms and inducible NO synthase
medicine
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comparison of the infectivity of arg- and wild-type Plasmodium berghei by inoculation of mice using sporozoites dissected from mosquito salivary glands shows a significant reduction in infectivity in the arg- strain 40 h postinfection
analysis
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arginase activity may interfere in nitric oxide activity assay. A nitric oxide synthase-independent radioactive signal in mitochondrial samples analyzed for nitric oxide synthase-catalyzed [14C]-L-arginine to [14C]-L-citrulline conversion is due to the arginase-catalyzed conversion of [14C]-L-arginine to [14C]-urea. The results, in addition to reconfirming the absence of nitric oxide synthase activity in rat liver MT, show the need to include arginase inhibitors in studies using mitochondrial samples in order to avoid confounding results when using nitric oxide synthase activity assays
medicine
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rejection of skin xenografts, but not allografts, is associated with a local high production of Th2 cytokines IL-4 and IL-10, overexpression of enzyme, strongly enhanced enzyme activity and attenuated NO generation in the graft. Upregulation of enzyme activity limits the bioavailability of L-arginine for the inducible NO synthase and thus attenuates generation of NO by the graft-infiltrating macrophages
medicine
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significant decrease of enzyme activity during 7th-21st day of gestation, significant increase in enzyme activity at term gestation, day 22. Gestational changes in enzyme activity negatively correlate with those in cyclic GMP production and positively correlate with those in endogenous NO synthase inhibitors and endothelin-1 contents. Enhanced enzyme activity at term gestation may be implicated in increasing myometrial contractions mediated by increase in endothelin-1
food industry
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when milk casein is hydrolyzed at 37C by using commercial digestive enzymes, pancreatin F and protease A, a significant accumulation of L-ornithine in the hydrolysate and the simultaneous disappearance of L-arginine is noted. Transient but distinct arginase activity, which is sufficiently high for L-ornithine production, is detected in the hydrolysate for a certain period during casein hydrolysis. Findings suggest that an inactive precursor of arginase is contaminated in pancreatin F and is proteolytically activated during the incubation
medicine
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H2O2 specifically impairs endothelium-dependent NO-mediated dilation of coronary microvessels by reducing L-arginine availability through upregulation of enzyme
medicine
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in coronary arteriole, enzyme activity increases twofold with hypertension. Inhibition of enzyme activity by Nomega-hydroxy-nor-L-arginine or incubation with L-arginine partially restores NO release and dilation to adenosine in hypertrophic vessels
medicine
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enzyme serves as a therapeutic target for the treatment of asthma, erectile dysfunction, and atherosclerosis
additional information
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pulmonary vascular and airway diseases in which arginase activity is increased are associated with decreased NO production and reduced smooth muscle relaxation