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| | <StructureSection load='4qxu' size='340' side='right'caption='[[4qxu]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='4qxu' size='340' side='right'caption='[[4qxu]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qxu]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QXU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QXU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qxu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QXU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QXU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ouu|4ouu]], [[4p3d|4p3d]], [[4p3c|4p3c]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4qxu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxu OCA], [https://pdbe.org/4qxu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qxu RCSB], [https://www.ebi.ac.uk/pdbsum/4qxu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qxu ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMP14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Membrane-type_matrix_metalloproteinase-1 Membrane-type matrix metalloproteinase-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.80 3.4.24.80] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qxu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qxu OCA], [http://pdbe.org/4qxu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qxu RCSB], [http://www.ebi.ac.uk/pdbsum/4qxu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qxu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == 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> | + | [https://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Membrane-type matrix metalloproteinase-1]]
| + | [[Category: Arroyo AG]] |
| - | [[Category: Arroyo, A G]] | + | [[Category: Cuiniasse P]] |
| - | [[Category: Cuiniasse, P]] | + | [[Category: Dive V]] |
| - | [[Category: Dive, V]] | + | [[Category: Dym O]] |
| - | [[Category: Dym, O]] | + | [[Category: Grossman M]] |
| - | [[Category: Grossman, M]] | + | [[Category: Moreno v]] |
| - | [[Category: ISPC, Israel Structural Proteomics Center]]
| + | [[Category: Rozenberg H]] |
| - | [[Category: Moreno, v]] | + | [[Category: Sagi I]] |
| - | [[Category: Rozenberg, H]] | + | [[Category: Solomonov I]] |
| - | [[Category: Sagi, I]] | + | [[Category: Udi Y]] |
| - | [[Category: Solomonov, I]] | + | |
| - | [[Category: Udi, Y]] | + | |
| - | [[Category: Igg fold]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Structural genomic]]
| + | |
| Structural highlights
Function
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.[1] [2]
Publication Abstract from PubMed
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.
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Golubkov VS, Chekanov AV, Cieplak P, Aleshin AE, Chernov AV, Zhu W, Radichev IA, Zhang D, Dong PD, Strongin AY. The Wnt/planar cell polarity protein-tyrosine kinase-7 (PTK7) is a highly efficient proteolytic target of membrane type-1 matrix metalloproteinase: implications in cancer and embryogenesis. J Biol Chem. 2010 Nov 12;285(46):35740-9. doi: 10.1074/jbc.M110.165159. Epub 2010, Sep 13. PMID:20837484 doi:http://dx.doi.org/10.1074/jbc.M110.165159
- ↑ Gu G, Zhao D, Yin Z, Liu P. BST-2 binding with cellular MT1-MMP blocks cell growth and migration via decreasing MMP2 activity. J Cell Biochem. 2012 Mar;113(3):1013-21. doi: 10.1002/jcb.23433. PMID:22065321 doi:10.1002/jcb.23433
- ↑ Udi Y, Grossman M, Solomonov I, Dym O, Rozenberg H, Moreno V, Cuniasse P, Dive V, Arroyo AG, Sagi I. Inhibition Mechanism of Membrane Metalloprotease by an Exosite-Swiveling Conformational Antibody. Structure. 2014 Dec 3. pii: S0969-2126(14)00357-8. doi:, 10.1016/j.str.2014.10.012. PMID:25482542 doi:http://dx.doi.org/10.1016/j.str.2014.10.012
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