Literature summary for 3.4.24.24 extracted from

Koo, B.; Kim, Y.; Han, J.; Kim, D.
Dimerization of matrix metalloproteinase-2 (MMP-2): functional implication in MMP-2 activation (2012), J. Biol. Chem., 287, 22643-22653.

Activating Compound

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.
(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