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Information on EC 2.5.1.61 - hydroxymethylbilane synthase and Organism(s) Homo sapiens

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EC Tree
IUBMB Comments
The enzyme works by stepwise addition of pyrrolylmethyl groups until a hexapyrrole is present at the active centre. The terminal tetrapyrrole is then hydrolysed to yield the product, leaving a cysteine-bound dipyrrole on which assembly continues. In the presence of a second enzyme, EC 4.2.1.75 uroporphyrinogen-III synthase, which is often called cosynthase, the product is cyclized to form uroporphyrinogen-III. If EC 4.2.1.75 is absent, the hydroxymethylbilane cyclizes spontaneously to form uroporphyrinogen I.
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
porphobilinogen deaminase, hmbs, hydroxymethylbilane synthase, pbg-d, uro-s, pbg deaminase, uroporphyrinogen i synthase, human porphobilinogen deaminase, uroporphyrinogen i synthetase, uroporphyrinogen synthase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
(HMB)-synthase
-
-
EC 4.3.1.8
-
formerly
hepatic porphobilinogen deaminase
-
human non-erythropoietic PBGD isoform
-
human PBGD
-
human porphobilinogen deaminase
-
hydroxymethylbilane synthase
-
PBG deaminase
PBG-D
-
-
PBG-deaminase
-
-
porphobilinogen ammonia-lyase (polymerizing)
-
-
-
-
porphobilinogen deaminase
pre-uroporphyrinogen synthase
-
-
-
-
preuroporphyrinogen synthase
-
synthase, uroporphyrinogen I
-
-
-
-
uPBGD
ubiquitous PBGD, espressed in all cells
UPGI-S
-
-
uroporphyrinogen I synthase
uroporphyrinogen I synthetase
-
-
uroporphyrinogen synthase
-
-
-
-
additional information
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH3
show the reaction diagram
catalytic cycle, cofactor assembly and tetrapyrrole chain polymerization mechanism, C261 is involved, residues D99 and R167 are essential for activity, overview
-
SYSTEMATIC NAME
IUBMB Comments
porphobilinogen:(4-[2-carboxyethyl]-3-[carboxymethyl]pyrrol-2-yl)methyltransferase (hydrolysing)
The enzyme works by stepwise addition of pyrrolylmethyl groups until a hexapyrrole is present at the active centre. The terminal tetrapyrrole is then hydrolysed to yield the product, leaving a cysteine-bound dipyrrole on which assembly continues. In the presence of a second enzyme, EC 4.2.1.75 uroporphyrinogen-III synthase, which is often called cosynthase, the product is cyclized to form uroporphyrinogen-III. If EC 4.2.1.75 is absent, the hydroxymethylbilane cyclizes spontaneously to form uroporphyrinogen I.
CAS REGISTRY NUMBER
COMMENTARY hide
9036-47-9
-
9074-91-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
4 porphobilinogen
uroporphyrinogen III + 4 NH3
show the reaction diagram
4 porphobilinogen + H2O
1-hydroxymethylbilane + 4 NH3
show the reaction diagram
4 porphobilinogen + H2O
hydroxylmethylbilane + 4 NH3
show the reaction diagram
4 porphobilinogen + H2O
hydroxymethylbilane + 4 NH3
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
4 porphobilinogen + H2O
1-hydroxymethylbilane + 4 NH3
show the reaction diagram
-
third reaction step in heme biosynthesis pathway
-
-
?
4 porphobilinogen + H2O
hydroxymethylbilane + 4 NH3
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dipyrromethane
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-methylopsopyrroledicarboxylic acid
-
-
Cd2+
-
12 mM, complete inhibition
Coproporphyrinogen
-
-
Cu2+
-
1 mM CuSO4, 87% inhibition
Fe2+
-
1 mM FeSO4, 58% inhibition
Fe3+
-
1 mM FeCl3, 62% inhibition
glycerol
-
15% inhibits 40% of enzyme activity
Hg2+
-
0.0004 mM HgCl2, 80% inhibition
isoporphobilinogen
-
-
N-ethylmaleimide
p-chloromercuribenzoate
-
0.002 mM, 74% inhibition
p-hydroxymercuribenzoate
-
-
Pb(NO3)2
-
0.005 mM, 35% inhibition
protoporphyrinogen
-
inhibits both erythroid and lymphoblast forms of the enzyme
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.051 - 0.077
Hydroxymethylbilane
0.00342 - 1.579
porphobilinogen
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.25
porphobilinogen
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000039
-
purified recombinant GST-tagged mutant enzyme
0.00117
-
-
0.002
R167Q mutant, pH 8.0
0.0128
-
40 kDa enzyme form
0.0183
-
42 kDa enzyme form
0.022
-
purified recombinant GST-tagged wild-type enzyme
0.023
wild type, pH 8.0
0.038
-
A form
0.039
-
B form
0.04
-
-
0.0402
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
phosphate buffer
7.8
-
mutant enzyme T59I
8
-
mutant enzyme V215M
additional information
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 9
-
pH 5.0: unstable below, pH 9.0 stable above
6 - 9
-
pH 6.0: no activity below, pH 9.0: 50% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45
-
activity twice that at 37°C
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
the addition of one molecule of porphobilinogen to the dipyrromethane cofactor is carried out in four steps: protonation of the substrate, porphobilinogen, deamination of porphobilinogen, electrophilic addition of the deaminated substrate to the terminal pyrrole ring of the enzyme-bound dipyrromethane cofactor and deprotonation of the carbon atom at the alpha-position of the second ring of dipyrromethane. Residue R26 is proposed to be the best suitable proton donor to the porphobilinogen moiety, which aids in the deamination of the substrate. During the electrophilic addition step, the intermediate formed is stabilized by the carboxylate side chain of the D99 residue. In the final deprotonation step, an extra proton from the second ring of dipyrromethane is transferred to R26 via the carboxylate side chain of D99, thus completing one cycle of the catalytic mechanism
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
HEM3_HUMAN
361
0
39330
Swiss-Prot
other Location (Reliability: 4)
A0A1W2PNU5_HUMAN
190
0
21250
TrEMBL
Mitochondrion (Reliability: 3)
A0A8I5KXV4_HUMAN
306
0
33499
TrEMBL
other Location (Reliability: 1)
F5H345_HUMAN
330
0
35761
TrEMBL
other Location (Reliability: 4)
F5H226_HUMAN
191
0
21279
TrEMBL
other Location (Reliability: 4)
A0A3B3IU34_HUMAN
218
0
24169
TrEMBL
other Location (Reliability: 4)
Q6LER4_HUMAN
17
0
1836
TrEMBL
other Location (Reliability: 2)
F1DBF3_HUMAN
22
0
2409
TrEMBL
other Location (Reliability: 4)
A0A3B3IU56_HUMAN
151
0
16775
TrEMBL
Mitochondrion (Reliability: 3)
F5GY90_HUMAN
187
0
20892
TrEMBL
Mitochondrion (Reliability: 3)
Q16812_HUMAN
40
0
4460
TrEMBL
other Location (Reliability: 5)
A0A3F2YNY7_HUMAN
355
0
38824
TrEMBL
other Location (Reliability: 4)
A0A3B3IRR1_HUMAN
338
0
37194
TrEMBL
Mitochondrion (Reliability: 3)
F5H0P4_HUMAN
228
0
25332
TrEMBL
Mitochondrion (Reliability: 3)
V9GZN3_HUMAN
11
0
964
TrEMBL
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25000
-
gel filtration
36000
37000
-
1 * 37000, SDS-PAGE, A and B form
38000
39500
-
1 * 39500, SDS-PAGE, B2 and B3
40000
-
1 * 40000, SDS-PAGE
41000
-
1 * 41000, SDS-PAGE
41200
-
1 * 41200, SDS-PAGE, erythrocyte enzyme
42000
44000
53000
GST-tagged recombinant p.Ala226ProfsX28, removing the GST tag produces a strongly degraded enzyme
68000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
additional information
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
molecular dynamics simulations reveal that the HMBS active-site loop movement and cofactor turn create space for the elongating pyrrole chain. Twenty-seven residues around the active site and water molecules interact to stabilize the large, negatively charged, elongating polypyrrole. Residues R26 and R167 are the strongest candidates for proton transfer to deaminate the incoming porphobilinogen molecules. R167 is a gatekeeper and facilitator of hydroxymethylbilane egress through the space between the enzyme's domains and the active-site loop
network analysis identifies 13 structural clusters persistent across five molecular dynamics trajectories corresponding to the five steps of pyrrole polymerization, which are responsible for maintaining the tertiary structure and domain arrangements of the enzyme. Amino acid residues R26 and F77 regulate the active site loop movement across the stages
vapor diffusion method, hanging drops with 20 mM Tris-HCl buffer, pH 8.2, containing 5 mM dithiothreitol and reservoir solution consisting of 0.6 M ammonium sulfate, 1.2 M lithium sulfate, 5% ethylene glycol, 50 mM sodium citrate, pH 5.6, and 50 mM dithiothreitol, diffraction data are collected at -173°C in 30% glycerol cryoprotected protein crystals
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
887insA
-
site-directed mutagenesis, the mutant shows reduced expression and subcellular distribution compared to the wild-type enzyme
A226P
A31P
0.6% of wild-type activity
A31T
0.50% of wild-type activity
D99H
3.3% of wild-type activity
E250D
G218R
0.1% of wild-type activity
G24S
c.70G>A (p.Gly24Ser)
G748A
-
site-directed mutagenesis, the mutant shows reduced expression and subcellular distribution compared to the wild-type enzyme
G748C
-
site-directed mutagenesis, the mutant shows reduced expression and subcellular distribution compared to the wild-type enzyme
H300L
c.899_900delinsTGCCTGCATCTG (p.His300LeuFsX10)
K132N
site-directed mutagenesis, the mutant shows no conformational or kinetic defect, no loss in relative activity (97% of wild-type activity) at standard conditions nor change in Vmax and Km. The mutation is not associated to acute intermittent porphyria, AIP
K98R
0.70% of wild-type activity
L170R
0.6% of wild-type activity
L170V
72.6% of wild-type activity
N169I
6.2% of wild-type activity
N322K
c.965_966insA (p.Asn322LysfsX36)
Q204K
c.610C>A, exon 10, missense mutation, 46% wild type activity, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
Q34K
0.2% of wild-type activity
Q34R
0.7% of wild-type activity
Q356E
95.7% of wild-type activity
R116W
site-directed mutagenesis, the mutant shows 0.5% of wild-type activity and defects in conformational stability. The mutation is associated to acute intermittent porphyria, AIP
R149L
0.1% of wild-type activity
R149Q
R149X
identification of a nonsense mutation in the PBGD gene on chromosome 11q23.3, which harbors the mutations causing acute intermittent porphyria, as the underlying genetic defect in Chester porphyria, phenotype, overview
R150I
0.02% of wild-type activity
R150Q
0.8% of wild-type activity
R167Q
R167W
R173Q
R173Q/Q204K
R173Q is more severe with a resulting enzyme activity of nearly zero, the Q204K increases the negative effect, particularly on the protein stability, 50 mM Tris-HCl, pH 8.2, 0.1% bovine serum albumin, 0.1% Triton, pH 8.2, 37°C, 1 h in the dark
R173W
R195C
3% of wild-type activity
R325A
c.972_973insG (p.Arg325AlafsX33)
R32P
c.95G>C (p.Arg32Pro)
R73Q/Q204K
a complex monoallelic mutation c.[518G>A; c.610C>A] (p.[Arg173Gln;p.Gln204Lys])
S146C
69.9% of wild-type activity
S146G
81% of wild-type activity
S146I
2.3% of wild-type activity
S147P
0.2% of wild-type activity
S165C
69.9% of wild-type activity
S262C
46.3% of wild-type activity
S28C
1.2% of wild-type activity
S28N
0.8 % of wild-type activity
S96F
1.0 % of wild-type activity
T145I
0.4% of wild-type activity
T145N
0.8% of wild-type activity
T58I
0.70% of wild-type activity
V215E
site-directed mutagenesis, the mutant shows 30% of wild-type activity and lower conformational stability and probably a perturbed elongation process, also 70% loss in both activity and Vmax. The mutation is associated to acute intermittent porphyria, AIP
V215M
-
19.4% residual activity compared to the wild type enzyme
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
56
-
2h, no loss of activity
60
-
2 h, 10% loss of activity
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
DTT stabilizes
phosphate stabilizes
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
photooxidation of the enzyme in the presence of methylene blue, 0.03%, and roes bengal, 0.03%, over a 5 min period, inhibits 90% and 60% of the enzyme activity, respectively
-
5883
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15°C, purified enzyme rapidely loses its activity
-
-20°C, forms A to E, stable for up to 18 months in 10 mM potassium phosphate buffer, pH 8.0, containing 0.2 mM dithioerythritol
-
4°C, purified enzyme stable for more than a month
-
erythrocytes lysates stored in 1 mM potassium phosphate, pH 7.6, containing 0.05% Trition X-100, 1 mM dithiothreitol and 1 mM MgCl2, no or little loss of activity after 1 year
-
purified enzyme loses its activity when it is frozen
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
2 forms
-
3 isoenzymes
-
5 forms, A: native enzyme, B-E: isomeres corresponding to the enzyme-substrate intermediates
-
blood samples are washed in phosphate buffered saline, liver rinsed in phosphate buffered saline
cell harvesting by centrifugation, washed, resuspended in NaCl-phosphate buffer containing of 140 mN NaCl, 2.7 mM KCl, 10 mM Na2HPO4, 1.8 mM KH2PO4, pH 7.3 with protease inhibitor cocktail, and 0.5% Triton X-100, lysis by shaking with lysozyme on ice, sonication, centrifugation, supernatant loaded onto glutathione sepharose 4B column, washed with 20 mM Tris-HCl, 100 mM NaCl, 1 mM EDTA, 0.5% Nonidet P-40+, pH 8.2, proteins eluted in 50 mM Tris-HCl, pH 8.3 buffer with 20 mM glutathione, thrombin digestion with thrombin at 20 U/mg protein at 20°C overnight, addition of glycerol to a concentration of 20%
cells centrifuged, washed with 0.9 M NaCl, re-centrifuged, washed with 20 mM Tris-HCl buffer, pH 8.2, with 5 mM dithiothreitol, and 200 microM PMSF, sonication, heating to 60°C under N2 gas, cooled to 4°C, supernatant applied to a Pharmacia 50 K/30 column packed with DEAE-Sephacel anion-exchange resin, equilibrated with 50 mM Tris-HCl buffer, pH 8.2 containing 5 mM dithiothreitol, and 100 microM PMSF, elution with 0-70 mM KCl gradient, active fractions are pooled and concentrated by ultrafiltration with a PM-10 membrane, further concentrated with a Centricon YM-10 centrifugal filter and gel-filtered on a Hiload 16/60 Superdex G-75 column, equilibrated with 100 mM Tris-HCl buffer, pH 8.2, containing 5 mM dithiothreitol and 100 microM PMSF, concentrated with a Centricon YM-10, buffer-exchanged into 20 mM Tris-HCl buffer, pH 8.2, containing 5 mM dithiothreitol with a Pharmacia PD10 column
glutathione Sepharose 4B column chromatography
-
partial
-
recombinant GST-tagged isoallelic forms K210 and E210 mutants from Escherichia coli to homogeneity
-
recombinant GST-tagged wild-type and mutant enzymes from Escherichia coli BL21 (DE3) by glutathione affinity chromatography, the GST-tag is cleaved off
-
recombinant GST-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) pLysS by glutathione affinity chromatgraphy, tag cleavage by thrombin, and ultrafiltration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloning and sequencing of naturally occurring mutants G11R and R173Q
-
Escherichia coli BL21(DE3) pLysS with pUHD2 plasmid
expressed in Escherichia coli BL21 cells
-
expression in Escherichia coli BL21(DE3) with pGEX-4T-1 expression vector
expression of wild-type and mutant enzymes in SH-SY5Y neuroblastoma cells, expression analysis
-
expression of wild-type and mutants in Escherichia coli strain BL21
-
localization of the porphobilinogen deaminase gene on chromosome 11q23.3
PBGD gene, DNA and amino acid sequence determination and analysis, expression of GST-tagged wild-type and mutant enzymes in Escherichia coli BL21 (DE3)
-
pTRE-EalAAT-hPBGD-WPRE plasmid from pTRE2 vector expressed in mice hepatocytes
recombinant expression of GST-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3) pLysS
the enzyme is expressed into a housekeeping or an erythroid form as a result of differential promoter usage and splicing, three pairs of isoallelic forms, expression of two of the isoallelic forms, K210 and E210, with mutations involved in acute intermittent porphyria, AIP, in Escherichia coli as GST fusion proteins
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
transfer of therapeutic plasmid with human enzyme into hepatocytes
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
medicine
pharmacology
-
safety, pharmacokinetics and pharmacodynamics of recombinant human porphobilinogen deaminase P 9808, administered to healthy subjects and asymptomatic porphobilinogen deaminase-deficient subjects with high concentrations of porphobilinogen, the substrate of porphobilinogen deaminase for investigation and establishing of an alternative therapy of acute intermittent porphyria, AIP, overview
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wright, D.J.; Lim, C.K.
Simultaneous determination of hydroxymethylbilane synthase and uroporphyrinogen III synthase in erythrocytes by high-performance liquid chromatography
Biochem. J.
213
85-88
1983
Homo sapiens
Manually annotated by BRENDA team
Frydman, R.B.; Feinstein, G.
Studies on porphobilinogen deaminase and uroporphyrinogen III cosynthase from human erythrocytes
Biochim. Biophys. Acta
350
358-373
1974
Homo sapiens
Manually annotated by BRENDA team
Miyagi, K.; Kaneshima, M.; Kawakami, J.; Nakada, F.; Petryka, Z.J.; Watson, C.J.
Uroporphyrinogen I synthetase from human erythrocytes: Separation, purification, and properties of isoenzymes
Proc. Natl. Acad. Sci. USA
76
6172-6176
1979
Bos taurus, Homo sapiens, Cereibacter sphaeroides, Spinacia oleracea
Manually annotated by BRENDA team
Anderson, P.M.; Desnick, R.J.
Purification and properties of uroporphyrinogen I synthase from human erythrocytes
J. Biol. Chem.
255
1993-1999
1980
Homo sapiens
Manually annotated by BRENDA team
Brown, R.C.; Elder, G.H.; Urquhart, A.J.
Purification of hydroxymethylbilane synthase from human erythrocytes
Biochem. Soc. Trans.
13
1227-1228
1985
Homo sapiens
-
Manually annotated by BRENDA team
Mazzetti, M.B.; Tomio, J.M.
Purification and some properties of rat liver uroporphyrinogen I synthase
Anal. Asoc. Quim. Argent.
76
207-215
1988
Chlorella regularis, Escherichia coli, Homo sapiens, Rattus norvegicus, Spinacia oleracea
-
Manually annotated by BRENDA team
Smythe, E.; Williams, D.C.
A simple rapid purification scheme for hydroxymethylbilane synthase from human erythrocytes
Biochem. J.
251
237-241
1988
Homo sapiens
Manually annotated by BRENDA team
Lannfelt, L.; Wetterberg, L.; Lilius, L.; Thunell, S.; Joernvall, H.; Pavlu, B.; Wielburski, A.; Gellerfors, P.
Porphobilinogen deaminase in human erythrocytes
Scand. J. Clin. Lab. Invest.
49
677-684
1989
Homo sapiens
Manually annotated by BRENDA team
Sharif, A.; Smith, A.G.; Abell, C.
Isolation and characterisation of cDNA clone for chlorophyll synthesis enzyme from Euglena gracilis
Eur. J. Biochem.
184
353-359
1989
Escherichia coli, Euglena gracilis, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Corrigall, A.V.; Meissner, P.N.; Kirsch, R.E.
Purification of human erythrocyte porphobilinogen deaminase
S. Afr. Med. J.
80
294-269
1991
Homo sapiens
Manually annotated by BRENDA team
Meissner, P.; Adams, P.; Kirsch, R.
Allosteric inhibition of human lymphoblast and purified porphobilinogen deaminase by protoporphyrinogen and coproporphyrinogen
J. Clin. Invest.
91
1436-1444
1993
Homo sapiens
Manually annotated by BRENDA team
Juknat, A.A.; Doernemann, D.; Senger, H.
Purification and kinetic studies on a porphobilinogen deaminase from the unicellular green alga Scenedesmus obliquus
Planta
193
123-130
1994
Saccharomyces cerevisiae, Chlorella regularis, Escherichia coli, Euglena gracilis, Homo sapiens, Pisum sativum, Rattus norvegicus, Cereibacter sphaeroides, Tetradesmus obliquus, Spinacia oleracea
-
Manually annotated by BRENDA team
Shoolingin-Jordan, P.M.; Al-Dbass, A.; McNeill, L.A.; Sarwar, M.; Butler, D.
Human porphobilinogen deaminase mutations in the investigation of the mechanism of dipyrromethane cofactor assembly and tetrapyrrole formation
Biochem. Soc. Trans.
31
731-735
2003
Homo sapiens
Manually annotated by BRENDA team
Schneider-Yin, X.; Hergersberg, M.; Schuurmans, M.M.; Gregor, A.; Minder, E.I.
Mutation hotspots in the human porphobilinogen deaminase gene: recurrent mutations G111R and R173Q occurring at CpG motifs
J. Inherit. Metab. Dis.
27
625-631
2004
Homo sapiens
Manually annotated by BRENDA team
Gruenberg-Etkovitz, N.; Greenbaum, L.; Grinblat, B.; Malik, Z.
Proteasomal degradation regulates expression of porphobilinogen deaminase (PBGD) mutants of acute intermittent porphyria
Biochim. Biophys. Acta
1762
819-827
2006
Homo sapiens
Manually annotated by BRENDA team
Sardh, E.; Rejkjaer, L.; Andersson, D.E.; Harper, P.
Safety, pharmacokinetics and pharmocodynamics of recombinant human porphobilinogen deaminase in healthy subjects and asymptomatic carriers of the acute intermittent porphyria gene who have increased porphyrin precursor excretion
Clin. Pharmacokinet.
46
335-349
2007
Homo sapiens
Manually annotated by BRENDA team
Poblete-Gutierrez, P.; Wiederholt, T.; Martinez-Mir, A.; Merk, H.F.; Connor, J.M.; Christiano, A.M.; Frank, J.
Demystification of Chester porphyria: a nonsense mutation in the porphobilinogen deaminase gene
Physiol. Res.
55 Suppl 2
S137-S144
2006
Homo sapiens (P08397)
Manually annotated by BRENDA team
Ulbrichova, D.; Flachsova, E.; Hrdinka, M.; Saligova, J.; Bazar, J.; Raman, C.S.; Martasek, P.
De Novo mutation found in the porphobilinogen deaminase gene in Slovak acute intermittent porphyria patient: molecular biochemical study
Physiol. Res.
55 Suppl 2
S145-S154
2006
Homo sapiens
Manually annotated by BRENDA team
Brons-Poulsen, J.; Christiansen, L.; Petersen, N.E.; Horder, M.; Kristiansen, K.
Characterization of two isoalleles and three mutations in both isoforms of purified recombinant human porphobilinogen deaminase
Scand. J. Clin. Lab. Invest.
65
93-105
2005
Homo sapiens
Manually annotated by BRENDA team
Wang, Y.; Scott, C.R.; Gelb, M.H.; Turecek, F.
Direct assay of enzymes in heme biosynthesis for the detection of porphyrias by tandem mass spectrometry. Porphobilinogen deaminase
Anal. Chem.
80
2606-2611
2008
Homo sapiens (P08397), Homo sapiens
Manually annotated by BRENDA team
Yang, C.C.; Kuo, H.C.; You, H.L.; Wang, J.; Huang, C.C.; Liu, C.Y.; Lan, M.Y.; Stephenson, D.A.; Lee, M.J.
HMBS mutations in Chinese patients with acute intermittent porphyria
Ann. Hum. Genet.
72
683-686
2008
Homo sapiens
Manually annotated by BRENDA team
Schneider-Yin, X.; Ulbrichova, D.; Mamet, R.; Martasek, P.; Marohnic, C.C.; Goren, A.; Minder, E.I.; Schoenfeld, N.
Characterization of two missense variants in the hydroxymethylbilane synthase gene in the Israeli population, which differ in their associations with acute intermittent porphyria
Mol. Genet. Metab.
94
343-346
2008
Homo sapiens
Manually annotated by BRENDA team
Ulbrichova-Douderova, D.; Martasek, P.
Detection of DNA variations in the polymorphic hydroxymethylbilane synthase gene by high-resolution melting analysis
Anal. Biochem.
395
41-48
2009
Homo sapiens (P08397)
Manually annotated by BRENDA team
Gill, R.; Kolstoe, S.E.; Mohammed, F.; Al D-Bass, A.; Mosely, J.E.; Sarwar, M.; Cooper, J.B.; Wood, S.P.; Shoolingin-Jordan, P.M.
Structure of human porphobilinogen deaminase at 2.8 A: the molecular basis of acute intermittent porphyria
Biochem. J.
420
17-25
2009
Homo sapiens (P08397), Homo sapiens
Manually annotated by BRENDA team
Ulbrichova, D.; Hrdinka, M.; Saudek, V.; Martasek, P.
Acute intermittent porphyria--impact of mutations found in the hydroxymethylbilane synthase gene on biochemical and enzymatic protein properties
FEBS J.
276
2106-2115
2009
Homo sapiens (P08397), Homo sapiens
Manually annotated by BRENDA team
Unzu, C.; Sampedro, A.; Mauleon, I.; Vanrell, L.; Dubrot, J.; de Salamanca, R.E.; Gonzalez-Aseguinolaza, G.; Melero, I.; Prieto, J.; Fontanellas, A.
Porphobilinogen deaminase over-expression in hepatocytes, but not in erythrocytes, prevents accumulation of toxic porphyrin precursors in a mouse model of acute intermittent porphyria
J. Hepatol.
52
417-424
2010
Homo sapiens (P08397), Homo sapiens, Mus musculus (P22907), Mus musculus
Manually annotated by BRENDA team
Bustad, H.; Vorland, M.; Roenneseth, E.; Sandberg, S.; Martinez, A.; Toska, K.
Conformational stability and activity analysis of two hydroxymethylbilane synthase mutants, K132N and V215E, with different phenotypic association with acute intermittent porphyria
Biosci. Rep.
33
617-626
2013
Homo sapiens (P08397)
Manually annotated by BRENDA team
Chakrabarty, B.; Das, D.; Bung, N.; Roy, A.; Bulusu, G.
Network analysis of hydroxymethylbilane synthase dynamics
J. Mol. Graph. Model.
99
107641
2020
Homo sapiens (P08397), Homo sapiens
Manually annotated by BRENDA team
Bung, N.; Roy, A.; Priyakumar, U.D.; Bulusu, G.
Computational modeling of the catalytic mechanism of hydroxymethylbilane synthase
Phys. Chem. Chem. Phys.
21
7932-7940
2019
Homo sapiens (P08397), Homo sapiens
Manually annotated by BRENDA team
Bung, N.; Roy, A.; Chen, B.; Das, D.; Pradhan, M.; Yasuda, M.; New, M.I.; Desnick, R.J.; Bulusu, G.
Human hydroxymethylbilane synthase Molecular dynamics of the pyrrole chain elongation identifies step-specific residues that cause AIP
Proc. Natl. Acad. Sci. USA
115
E4071-E4080
2018
Homo sapiens (P08397), Homo sapiens
Manually annotated by BRENDA team