4qxu

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== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/MMP14_HUMAN MMP14_HUMAN]] Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15.<ref>PMID:20837484</ref> <ref>PMID:22065321</ref>
[[http://www.uniprot.org/uniprot/MMP14_HUMAN MMP14_HUMAN]] Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15.<ref>PMID:20837484</ref> <ref>PMID:22065321</ref>
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== Publication Abstract from PubMed ==
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Membrane type 1 metalloprotease (MT1-MMP) is a membrane-anchored, zinc-dependent protease. MT1-MMP is an important mediator of cell migration and invasion, and overexpression of this enzyme has been correlated with the malignancy of various tumor types. Therefore, modulators of MT1-MMP activity are proposed to possess therapeutic potential in numerous invasive diseases. Here we report the inhibition mode of MT1-MMP by LEM-2/15 antibody, which targets a surface epitope of MT1-MMP. Specifically, the crystal structures of Fab LEM-2/15 in complex with the MT1-MMP surface antigen suggest that conformational swiveling of the enzyme surface loop is required for effective binding and consequent inhibition of MT1-MMP activity on the cell membrane. This inhibition mechanism appears to be effective in controlling active MT1-MMP in endothelial cells and at the leading edge of migratory cancer cells.
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Inhibition Mechanism of Membrane Metalloprotease by an Exosite-Swiveling Conformational Antibody.,Udi Y, Grossman M, Solomonov I, Dym O, Rozenberg H, Moreno V, Cuniasse P, Dive V, Arroyo AG, Sagi I Structure. 2014 Dec 3. pii: S0969-2126(14)00357-8. doi:, 10.1016/j.str.2014.10.012. PMID:25482542<ref>PMID:25482542</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
== References ==
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Revision as of 09:30, 31 December 2014

Novel Inhibition Mechanism of Membrane Metalloprotease by an Exosite-Swiveling Conformational antibody

4qxu, resolution 2.30Å

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