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Information on EC 3.4.24.46 - adamalysin
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3.4.24.46 adamalysinSpecify your search results
Word Map
- 3.4.24.46
- metalloproteinases
-
disintegrin
-
snake
-
metzincins
-
electrotransfer
- adam15
- astacins
- matrixins
- alpha-secretase
-
met-turn
-
hexxhxxgxxh
- medicine
The enzyme appears in viruses and cellular organisms
Reaction Schemes
Cleavage of Phe1-/-Val, His5-/-Leu, His10-/-Leu, Ala14-/-Leu, Leu15-/-Tyr, and Tyr16-/-Leu of insulin B chain
Synonyms
adamalysin, adamalysin ii, metargidin, proteinase i and ii, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Adamalysin II
Crotalus adamanteus metalloendopeptidase
-
-
-
-
Crotalus adamanteus venom proteinase II
-
-
-
-
Proteinase I and II
-
-
-
-
Proteinase, Crotalus adamanteus venom, II
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-
-
-
Adamalysin II
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cleavage of Phe1-/-Val, His5-/-Leu, His10-/-Leu, Ala14-/-Leu, Leu15-/-Tyr, and Tyr16-/-Leu of insulin B chain
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-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
74812-51-4
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
human plasma alpha1-proteinase inhibitor + H2O
hydrolyzed and inactivated human plasma alpha1-proteinase inhibitor
Oxidized insulin B-chain + H2O
?
-
cleavage at Phe1-Val2, His5-Leu6, His10-Leu11, Ala14-Leu15, Leu15-Tyr16 and Tyr16-Leu17
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-
?
Polyarginine + H2O
Hydrolyzed polyarginine
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-
chain length 6-12 amino acids, not arginine monomers
?
Polylysine + H2O
Hydrolyzed polylysine
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-
chain length 6-12 amino acids, not lysine monomers
?
Human antithrombin III + H2O
Hydrolyzed and inactivated antithrombin III
-
in the presence of heparin non-inactivating cleavage in aminoterminal region at Glu37-Gln38 followed by inactivating cleavages in carboxyterminal region at Ala375-Ser376 and Ala378-Val379, in the absence of heparin inactivating cleavage in carboxyterminal region at Ser383-Ala384
first occuring fragment in the presence of heparin is a still active antithrombin of MW 56000, followed by inactive fragments of MW 50000 and MW 5000, in the absence of heparin only inactive fragments of MW 56000 and MW 5000 occur
?
Human antithrombin III + H2O
Hydrolyzed and inactivated antithrombin III
-
MW 60000, at a molar ratio of antithrombin III:enzyme of 40:1, in the presence and absence of heparin
first occuring fragment in the presence of heparin is a still active antithrombin of MW 56000, followed by inactive fragments of MW 50000 and MW 5000, in the absence of heparin only inactive fragments of MW 56000 and MW 5000 occur
?
human plasma alpha1-proteinase inhibitor + H2O
hydrolyzed and inactivated human plasma alpha1-proteinase inhibitor
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no hydrolysis in the presence of alpha1-macroglobulin
-
-
?
human plasma alpha1-proteinase inhibitor + H2O
hydrolyzed and inactivated human plasma alpha1-proteinase inhibitor
-
MW 54000, native and heat-denatured, the latter is more extensively hydrolyzed
MW 50000 and MW 4000 fragments
?
additional information
?
-
-
no hydrolysis of benzoyl-L-Arg ethyl ester, benzoyl-L-Tyr ethyl ester
-
-
?
additional information
?
-
-
snake venom zincendopeptidase, hydrolyzes basement membrane proteins involved in the adhesion among capillary endothelial cells, inducing extensive haemorrhages in the bitten preys
-
?
additional information
?
-
-
disintegrin domain of enzyme acts as inhibitor of angiogenesis, tumor growth, and metastasis
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
-
snake venom zincendopeptidase, hydrolyzes basement membrane proteins involved in the adhesion among capillary endothelial cells, inducing extensive haemorrhages in the bitten preys
-
?
additional information
?
-
-
disintegrin domain of enzyme acts as inhibitor of angiogenesis, tumor growth, and metastasis
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Zn2+
Zn2+
-
zinc-binding motif, almost tetrahedrally co-ordinated by His142, His146 and His152 and a water molecule anchored to an intermediate Glu residue, Glu143
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
2 mM Zn2+ protects at 2 mM 2-mercaptoethanol, 2 mM Zn2+ partially protects at 10-50 mM 2-mercaptoethanol, 2 mM Ca2+ partially protects at 2-10 mM 2-mercaptoethanol, no protection at 50 mM 2-mercaptoethanol
Pro-Lys-Met-D-Cys-Gly-Val-NH2
-
less effective than Pro-Lys-Met-Cys-Gly-Val-NH2
cysteine
-
2 mM Zn2+ protects at 2 mM cysteine, protects partially at 10 mM cysteine, no protection at 20 mM cysteine
EDTA
-
2 mM Zn2+ protects at 0.5-1 mM EDTA, no protection at 2 mM EDTA, 2 mM Ca2+ partially protects at 0.5 mM EDTA, weakly at 1 mM EDTA, no protection at 2 mM EDTA; hide powder azure or alpha1-proteinase inhibitor as substrates
GSH
-
2 mM Zn2+ or Ca2+ protects at 2 mM GSH, partially protects at 10 mM GSH, no protection at 50 mM GSH
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
heparin
-
activation, acceleration of antithrombin III inactivation, at a ratio of 6.7:1 (w/w)
additional information
-
activation of inactive adamalysin II zymogen by cystein-switch-like mechanism
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma
Inhibitory antibodies against endopeptidase activity of human adamalysin 19.
Carcinoma
Metargidin, a membrane-anchored metalloprotease-disintegrin protein with an RGD integrin binding sequence.
Melanoma
Biological Properties of Melanoma and Endothelial Cells after Plasmid AMEP Gene Electrotransfer Depend on Integrin Quantity on Cells.
Melanoma
Gene electrotransfer of plasmid AMEP, an integrin-targeted therapy, has antitumor and antiangiogenic action in murine B16 melanoma.
Melanoma
Gene Electrotransfer of Plasmid Antiangiogenic Metargidin Peptide (AMEP) in Disseminated Melanoma: Safety and Efficacy Results of a Phase I First-in-Man Study.
Neoplasms
Alternative splicing of ADAM15 regulates its interactions with cellular SH3 proteins.
Neoplasms
Characterization of growth factor-induced serine phosphorylation of tumor necrosis factor-alpha converting enzyme and of an alternatively translated polypeptide.
Neoplasms
P2Y2 nucleotide receptors mediate metalloprotease-dependent phosphorylation of epidermal growth factor receptor and ErbB3 in human salivary gland cells.
Neoplasms
Regulation of tumor necrosis factor-alpha and tumor necrosis factor converting enzyme in human osteoarthritis.
Neoplasms
Structures of adamalysin II with peptidic inhibitors. Implications for the design of tumor necrosis factor alpha convertase inhibitors.
Neoplasms
The secretases that cleave angiotensin converting enzyme and the amyloid precursor protein are distinct from tumour necrosis factor-alpha convertase.
Oligodendroglioma
Microvesicles shed by oligodendroglioma cells and rheumatoid synovial fibroblasts contain aggrecanase activity.
Osteoarthritis
Interleukin 13 (IL-13)-regulated expression of the chondroprotective metalloproteinase ADAM15 is reduced in aging cartilage.
Osteoarthritis
Regulation of tumor necrosis factor-alpha and tumor necrosis factor converting enzyme in human osteoarthritis.
Purpura, Thrombotic Thrombocytopenic
Complement activation in diseases presenting with thrombotic microangiopathy.
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Eastern diamondback rattlesnake
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). VM12_CROAD
203
0
23076
Swiss-Prot
Mitochondrion (Reliability: 5)
Q7LZP2_CROAD
203
0
23310
TrEMBL
Mitochondrion (Reliability: 5)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
24000
additional information
additional information
-
amino acid sequence compared to other adamalysins
additional information
-
shares a similar overall topology with astacin, with the collagenase catalytic domains and the Pseudomonas aeruginosa alkaline proteinase and exhibits a virtual identical zinc environment with these other metzincins
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
complex with phosphate inhibitor, crystals obtained by sitting drop vapour diffusion technique, space group P3(2)12, cell parameters a : b : 73.5 A, c : 96.9 A
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
recombinant disintegrin domain of enzyme, shows inhibitory activities on endothelial cell proliferation and adhesion on the integrin substrates fibronectin, vitronectin, and fibrinogen.The domain totally abrogates endothelial cell migration and blocks most capillary formation in a three-dimensional fibrin gel. Athymic mice bearing electrotransferred domain exhibit strong inhibition of tumor angiogenesis
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
recombinant disintegrin domain of enzyme, shows inhibitory activities on endothelial cell proliferation and adhesion on the integrin substrates fibronectin, vitronectin, and fibrinogen.The domain totally abrogates endothelial cell migration and blocks most capillary formation in a three-dimensional fibrin gel. Athymic mice bearing electrotransferred domain exhibit strong inhibition of tumor angiogenesis
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bode, W.; Gomis-Ruth, F.X.; Stckler, W.
Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the metzincins
FEBS Lett.
331
134-140
1993
Crotalus adamanteus
brenda
Kurecki, T.; Laskowski, M.; Kress, L.F.
Purification and some properties of two proteinases from Crotalus adamanteus venom that inactivate human alpha 1-proteinase inhibitor
J. Biol. Chem.
253
8340-8345
1978
Crotalus adamanteus
brenda
Kress, L.F.; Kurecki, T.
Studies on the complex between human alpha 2-macroglobulin and Crotalus adamanteus proteinase II. Release of active proteinase from the complex
Biochim. Biophys. Acta
613
469-475
1980
Crotalus adamanteus
brenda
Kress, L.F.; Catanese, J.J.
Identification of the cleavage sites resulting from enzymatic inactivation of human antithrombin III by Crotalus adamanteus proteinase II in the the presence and absence of heparin
Biochemistry
20
7432-7438
1981
Crotalus adamanteus
brenda
Grams, F.; Huber, R.; Kress, L.F.; Moroder, L.; Bode, W.
Activation of snake venom metalloproteinases by a cysteine switch-like mechanism
FEBS Lett.
335
76-80
1993
Crotalus adamanteus
brenda
Gomis-Ruth, F.X.; Kress, L.F.; Kellermann, J.; Mayr, I.; Lee, X.; Huber, R.; Bode, W.
Refined 2.0 A X-ray crystal structure of the snake venom zinc-endopeptidase adamalysin II. Primary and tertiary structure determination, refinement, molecular structure and comparison with astacin, collagenase and thermolysin
J. Mol. Biol.
239
513-544
1994
Crotalus adamanteus
brenda
Bode, W.; Kress, L.F.
Crystallization and preliminary x-ray diffraction data of proteinase II from Crotalus adamanteus (eastern diamond rattlesnake)
FEBS Lett.
154
274-276
1983
Crotalus adamanteus
-
brenda
D'Alessio, S.; Gallina, C.; Gavuzzo, E.; Giordano, C.; Gorini, B.; Mazza, F.; Paradisi, M.P.; Panini, G.; Pochetti, G.; Sella, A.
Inhibition of adamalysin II and MMPs by phosphonate analogues of snake venom peptides
Bioorg. Med. Chem.
7
389-394
1999
Crotalus adamanteus
brenda
Cirilli, M.; Gallina, C.; Gavuzzo, E.; Giordano, C.; Gomis-Ruth, F.X.; Gorini, B.; Kress, L.F.; Mazza, F.; Paradisi, M.P.; Pochetti, G.; Politi, V.
2 angstrom X-ray structure of adamalysin II complexed with a peptide phosphonate inhibitor adopting a retro-binding mode
FEBS Lett.
418
319-322
1997
Crotalus adamanteus
brenda
Gomis-Rueth, F.X.; Meyer, E.F.; Kress, L.F.; Politi, V.
Structures of adamalysin II with peptidic inhibitors. Implications for the design of tumor necrosis factor alpha convertase inhibitors
Protein Sci.
7
283-292
1998
Crotalus adamanteus
brenda
Trochon-Joseph, V.; Martel-Renoir, D.; Mir, L.M.; Thomaidis, A.; Opolon, P.; Connault, E.; Li, H.; Grenet, C.; Fauvel-Lafeve, F.; Soria, J.; Legrand, C.; Soria, C.; Perricaudet, M.; Lu, H.
Evidence of antiangiogenic and antimetastatic activities of the recombinant disintegrin domain of metargidin
Cancer Res.
64
2062-2069
2004
Homo sapiens
brenda
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