Information on EC 3.4.24.46 - adamalysin

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The expected taxonomic range for this enzyme is: Amniota

EC NUMBER
COMMENTARY
3.4.24.46
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RECOMMENDED NAME
GeneOntology No.
adamalysin
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Cleavage of Phe1-/-Val, His5-/-Leu, His10-/-Leu, Ala14-/-Leu, Leu15-/-Tyr, and Tyr16-/-Leu of insulin B chain
show the reaction diagram
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-
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REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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-
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SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Adamalysin II
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-
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Crotalus adamanteus metalloendopeptidase
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-
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Crotalus adamanteus venom proteinase II
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metargidin
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Proteinase I and II
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Proteinase, Crotalus adamanteus venom, II
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CAS REGISTRY NUMBER
COMMENTARY
74812-51-4
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ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
recombinant disintegrin domain of enzyme
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Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
casein + H2O
?
show the reaction diagram
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-
-
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hide powder azure + H2O
?
show the reaction diagram
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-
-
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Human antithrombin III + H2O
Hydrolyzed and inactivated antithrombin III
show the reaction diagram
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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, 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
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human plasma alpha1-proteinase inhibitor + H2O
hydrolyzed and inactivated human plasma alpha1-proteinase inhibitor
show the reaction diagram
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no hydrolysis in the presence of alpha1-macroglobulin
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-
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Oxidized insulin B-chain + H2O
?
show the reaction diagram
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cleavage at Phe1-Val2, His5-Leu6, His10-Leu11, Ala14-Leu15, Leu15-Tyr16 and Tyr16-Leu17
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Polyarginine + H2O
Hydrolyzed polyarginine
show the reaction diagram
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chain length 6-12 amino acids, not arginine monomers
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Polylysine + H2O
Hydrolyzed polylysine
show the reaction diagram
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chain length 6-12 amino acids, not lysine monomers
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human plasma alpha1-proteinase inhibitor + H2O
hydrolyzed and inactivated human plasma alpha1-proteinase inhibitor
show the reaction diagram
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MW 54000, native and heat-denatured, the latter is more extensively hydrolyzed
MW 50000 and MW 4000 fragments
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additional information
?
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no hydrolysis of benzoyl-L-Arg ethyl ester, benzoyl-L-Tyr ethyl ester
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additional information
?
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snake venom zincendopeptidase, hydrolyzes basement membrane proteins involved in the adhesion among capillary endothelial cells, inducing extensive haemorrhages in the bitten preys
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?
additional information
?
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disintegrin domain of enzyme acts as inhibitor of angiogenesis, tumor growth, and metastasis
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
additional information
?
-
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snake venom zincendopeptidase, hydrolyzes basement membrane proteins involved in the adhesion among capillary endothelial cells, inducing extensive haemorrhages in the bitten preys
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?
additional information
?
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disintegrin domain of enzyme acts as inhibitor of angiogenesis, tumor growth, and metastasis
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METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Ca2+
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metalloproteinase
Ca2+
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calcium binding site; metalloproteinase
Zn2+
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zinc containing metalloproteinase
Zn2+
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zinc-binding motif, almost tetrahedrally co-ordinated by His142, His146 and His152 and a water molecule anchored to an intermediate Glu residue, Glu143; zinc-endopeptidase
Zn2+
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zinc endopeptidase
Zn2+
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zincendopeptidase
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
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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
Acetyl-Trp-Cys-Gly-Pro-NH2
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alpha1-Macroglobulin
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mechanism
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cysteine
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2 mM Zn2+ protects at 2 mM cysteine, protects partially at 10 mM cysteine, no protection at 20 mM cysteine
EDTA
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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
Fur-Leu-Trp-OH
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GSH
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2 mM Zn2+ or Ca2+ protects at 2 mM GSH, partially protects at 10 mM GSH, no protection at 50 mM GSH
Lys-Pro-Arg-Cys-Gly-Val-NH2
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N-(furan-2-yl)carbonyl-L-leucyl-D-phosphotryptophan
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N-(furan-2-yl)carbonyl-L-leucyl-L-phosphotryptophan
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N-(furan-2-yl)carbonyl-Leu-Trp(P)-(OH)2
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Pro-Lys-Met-Cys-Gly-Val-NH2
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strong
Pro-Lys-Met-D-Cys-Gly-Val-NH2
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less effective than Pro-Lys-Met-Cys-Gly-Val-NH2
Pro-Lys-Met-Ser-Gly-Val-NH2
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weak
PyroGlu-Asn-Trp
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naturally found endogenous venom tripeptide inhibitor
Lys-Thr-Phe-Thr-Ser-Cys
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additional information
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no inhibition by diisopropyl fluorophosphate
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ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
heparin
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activation, acceleration of antithrombin III inactivation, at a ratio of 6.7:1 (w/w)
additional information
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activation of inactive adamalysin II zymogen by cystein-switch-like mechanism
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SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
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pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
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alkaline assay conditions
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
23
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assay at
25
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assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
22400
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Crotalus adamanteus, sedimentation equilibrium centrifugation
23750
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Crotalus adamanteus, calculated from amino acid content
24000
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Crotalus adamanteus, PAGE
additional information
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amino acid composition compared to proteinase I
additional information
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amino acid sequence compared to other adamalysins; primary and tertiary structure; 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
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
monomer
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1 * 24000, Crotalus adamanteus, SDS-PAGE
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
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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Crotalus adamanteus
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Crotalus adamanteus; structure
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crystal structure in complex with 2 inhibitors
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STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-18°C, in 0.05 M sodium borate, pH 8, 2 mM CaCl2, at least 6 months
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Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
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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
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
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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