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| | ==Transient Collagen Triple Helix Binding to a Key Metalloproteinase in Invasion and Development: Spin Labels to Structure== | | ==Transient Collagen Triple Helix Binding to a Key Metalloproteinase in Invasion and Development: Spin Labels to Structure== |
| - | <StructureSection load='2mqs' size='340' side='right'caption='[[2mqs]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | + | <StructureSection load='2mqs' size='340' side='right'caption='[[2mqs]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mqs]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MQS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MQS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mqs]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MQS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MQS FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMP14 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Membrane-type_matrix_metalloproteinase-1 Membrane-type matrix metalloproteinase-1], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2mqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mqs OCA], [https://pdbe.org/2mqs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mqs RCSB], [https://www.ebi.ac.uk/pdbsum/2mqs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mqs ProSAT]</span></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=2mqs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mqs OCA], [https://pdbe.org/2mqs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mqs RCSB], [https://www.ebi.ac.uk/pdbsum/2mqs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mqs ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [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: Membrane-type matrix metalloproteinase-1]] | + | [[Category: Marcink T]] |
| - | [[Category: Doren, S R.Van]] | + | [[Category: Van Doren SR]] |
| - | [[Category: Marcink, T]]
| + | [[Category: Zhao Y]] |
| - | [[Category: Zhao, Y]] | + | |
| - | [[Category: Hydrolase]]
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| - | [[Category: Protein/protein]]
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| 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
Skeletal development and invasion by tumor cells depends on proteolysis of collagen by the pericellular metalloproteinase MT1-MMP. Its hemopexin-like (HPX) domain binds to collagen substrates to facilitate their digestion. Spin labeling and paramagnetic nuclear magnetic resonance (NMR) detection have revealed how the HPX domain docks to collagen I-derived triple helix. Mutations impairing triple-helical peptidase activity corroborate the interface. Saturation transfer difference NMR suggests rotational averaging around the longitudinal axis of the triple-helical peptide. Part of the interface emerges as unique and potentially targetable for selective inhibition. The triple helix crosses the junction of blades I and II at a 45 degrees angle to the symmetry axis of the HPX domain, placing the scissile Gly approximately Ile bond near the HPX domain and shifted approximately 25 A from MMP-1 complexes. This raises the question of the MT1-MMP catalytic domain folding over the triple helix during catalysis, a possibility accommodated by the flexibility between domains suggested by atomic force microscopy images.
Transient collagen triple helix binding to a key metalloproteinase in invasion and development.,Zhao Y, Marcink TC, Sanganna Gari RR, Marsh BP, King GM, Stawikowska R, Fields GB, Van Doren SR Structure. 2015 Feb 3;23(2):257-69. doi: 10.1016/j.str.2014.11.021. PMID:25651059[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Zhao Y, Marcink TC, Sanganna Gari RR, Marsh BP, King GM, Stawikowska R, Fields GB, Van Doren SR. Transient collagen triple helix binding to a key metalloproteinase in invasion and development. Structure. 2015 Feb 3;23(2):257-69. doi: 10.1016/j.str.2014.11.021. PMID:25651059 doi:http://dx.doi.org/10.1016/j.str.2014.11.021
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