Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | heparan sulfate is required for thrombin-mediated activation of pro-MMP-2 by binding to thrombin, presumably through conformational changes at the active site of the enzyme. Homodimerization of the enzyme enhances thrombin-mediated activation of pro-MMP-2. Enzyme residue Cys102 plays a role in inhibition of catalytic activity through a cysteine-zinc ion pairing, this pairing is disrupted by the intermolecular disulfide bond in the MMP-2 homodimer, resulting in enzyme activation. Disruption of the cysteine-zinc ion pairing by homodimerization of MMP-2 opens the active site, but it may accommodate only small peptide substrates. Thus, MMP-2 propeptide processing is a prerequisite to gain its proteolytic activity against large substrates, including gelatin | Homo sapiens |
Cloned (Comment) | Organism |
---|---|
recombinant expression of wild-type and mutant full-length MMP-2 or MMP-2 with C-terminal Myc and His tags in COS-1 cells, secretion of the enzyme to the cell culture medium | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
C102S | site-directed mutagenesis | Homo sapiens |
C233S | site-directed mutagenesis | Homo sapiens |
C247S | site-directed mutagenesis | Homo sapiens |
C259S | site-directed mutagenesis | Homo sapiens |
C274S | site-directed mutagenesis | Homo sapiens |
C291S | site-directed mutagenesis | Homo sapiens |
C305S | site-directed mutagenesis | Homo sapiens |
C317S | site-directed mutagenesis | Homo sapiens |
C332S | site-directed mutagenesis | Homo sapiens |
C349S | site-directed mutagenesis | Homo sapiens |
C363S | site-directed mutagenesis | Homo sapiens |
C375S | site-directed mutagenesis | Homo sapiens |
C395S | site-directed mutagenesis | Homo sapiens |
C60S | site-directed mutagenesis | Homo sapiens |
C65S | site-directed mutagenesis | Homo sapiens |
E404A | proteolytically inactive pro-MMP-2 mutant | Homo sapiens |
S160A | site-directed mutagenesis | Homo sapiens |
S365A | site-directed mutagenesis | Homo sapiens |
S575A | site-directed mutagenesis | Homo sapiens |
S644A | site-directed mutagenesis | Homo sapiens |
S647A | site-directed mutagenesis | Homo sapiens |
T250A | site-directed mutagenesis | Homo sapiens |
T354A | site-directed mutagenesis | Homo sapiens |
T377A/T378A | site-directed mutagenesis | Homo sapiens |
T455A | site-directed mutagenesis | Homo sapiens |
T73A | site-directed mutagenesis | Homo sapiens |
T96A | site-directed mutagenesis | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | enzyme residue Cys102 plays a role in inhibition of catalytic activity through a cysteine-zinc ion pairing, this pairing is disrupted by the intermolecular disulfide bond in the MMP-2 homodimer, resulting in enzyme activation. Disruption of the cysteine-zinc ion pairing by homodimerization of MMP-2 opens the active site, but it may accommodate only small peptide substrates. Thus, MMP-2 propeptide processing is a prerequisite to gain its proteolytic activity against large substrates, including gelatin | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Ca2+ | Ca2+is essential for homodimerization of enzyme MMP-2, analysis, detailed overview | Homo sapiens | |
Zn2+ | a catalytic zinc ion bound in the active site | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
Gelatin + H2O | Homo sapiens | - |
? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P08253 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
proteolytic modification | thrombin directly cleaves the propeptide of MMP-2 at specific sites, on the C-terminal side of Arg98 and Arg101 with a preference for Arg101, for enzyme activation. Heparan sulfate is required for thrombin-mediated activation of pro-MMP-2 by binding to thrombin, presumably through conformational changes at the active site of the enzyme. Homodimerization of MMP-2 enhances thrombin-mediated activation of pro-MMP-2 | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
(7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-DPA-Ala-Arg-NH2 + H2O | - |
Homo sapiens | (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly + Leu-DPA-Ala-Arg-NH2 | - |
? | |
Gelatin + H2O | - |
Homo sapiens | ? | - |
? | |
Gelatin + H2O | fluorescein-conjugated gelatin | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
homodimer | homodimerization of enzyme MMP-2, through an intermolecular disulfide bond between Cys102 and the neighboring Cys102, requires Ca2+ but is not associated with protein kinase C-mediated phosphorylation. The cleavage is followed by intermolecular autoproteolytic cleavage at the Asn109-Tyr peptide bond, resulting in full enzymatic activation. Homodimerization of the enzyme enhances thrombin-mediated activation of pro-MMP-2 | Homo sapiens |
More | enzyme MMP-2 forms heterodimers with various proteins, including TIMP-2, TIMP-3, TIMP-4, and glycosaminoglycans | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
matrix metalloproteinase-2 | - |
Homo sapiens |
MMP-2 | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
additional information | enzyme MMP-2 forms heterodimers with various proteins, including TIMP-2, TIMP-3, TIMP-4, and glycosaminoglycans. Disruption of the cysteine-zinc ion pairing by homodimerization of MMP-2 opens the active site, but it may accommodate only small peptide substrates. Thus, MMP-2 propeptide processing is a prerequisite to gain its proteolytic activity against large substrates, including gelatin | Homo sapiens |