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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/MMP2_HUMAN MMP2_HUMAN] Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</ref>  PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</ref>  Isoform 2: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</ref>  
[https://www.uniprot.org/uniprot/MMP2_HUMAN MMP2_HUMAN] Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</ref>  PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</ref>  Isoform 2: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.<ref>PMID:9476898</ref> <ref>PMID:10559137</ref> <ref>PMID:11029402</ref> <ref>PMID:11751392</ref> <ref>PMID:11710594</ref> <ref>PMID:19493954</ref> <ref>PMID:22509276</ref>  
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== Publication Abstract from PubMed ==
Unlike other synthetic or physiological inhibitors for matrix metalloproteinases (MMPs), the beta-amyloid precursor protein-derived inhibitory peptide (APP-IP) having ISYGNDALMP sequence has a high selectivity toward MMP-2. Our previous study identified amino acid residues of MMP-2 essential for its selective inhibition by APP-IP, and also demonstrated that the N to C direction of the decapeptide inhibitor relative to the substrate-binding cleft of MMP-2 is opposite to that of substrate. However, detailed interactions between the two molecules remained to be clarified. Here, we determined the crystal structure of the catalytic domain of MMP-2 in complex with APP-IP. We found that APP-IP in the complex is indeed embedded into the substrate-binding cleft of the catalytic domain in the N to C direction opposite to that of substrate. With the crystal structure, it was first clarified that the aromatic side chain of Tyr(3) of the inhibitor is accommodated into the S1' pocket of the protease, and the carboxylate group of Asp(6) of APP-IP coordinates bidentately to the catalytic zinc of the enzyme. The Ala(7) to Pro(10) and Tyr(3) to Ile(1) strands of the inhibitor extend into the non-prime and the prime sides of the cleft, respectively. Therefore, the decapeptide inhibitor has long-range contact with the substrate-binding cleft of the protease. This mode of interaction is probably essential for the high MMP-2-selectivity of the inhibitor, because MMPs share a common architecture in the vicinity of the catalytic center but whole structures of their substrate-binding clefts have sufficient variety for the inhibitor to distinguish MMP-2 from other MMPs.
Structural basis for matrix metalloproteinase-2 (MMP-2)-selective inhibitory action of {beta}-amyloid precursor protein-derived inhibitor.,Hashimoto H, Takeuchi T, Komatsu K, Miyazaki K, Sato M, Higashi S J Biol Chem. 2011 Aug 3. PMID:21813640<ref>PMID:21813640</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
==See Also==

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