4qxu: Difference between revisions
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==Novel Inhibition Mechanism of Membrane Metalloprotease by an Exosite-Swiveling Conformational antibody== | |||
<StructureSection load='4qxu' size='340' side='right'caption='[[4qxu]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</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='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> | |||
</table> | |||
== 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> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:25482542</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4qxu" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Arroyo AG]] | |||
[[Category: Cuiniasse P]] | |||
[[Category: Dive V]] | |||
[[Category: Dym O]] | |||
[[Category: Grossman M]] | |||
[[Category: Moreno v]] | |||
[[Category: Rozenberg H]] | |||
[[Category: Sagi I]] | |||
[[Category: Solomonov I]] | |||
[[Category: Udi Y]] | |||
Latest revision as of 20:40, 20 September 2023
Novel Inhibition Mechanism of Membrane Metalloprotease by an Exosite-Swiveling Conformational antibodyNovel Inhibition Mechanism of Membrane Metalloprotease by an Exosite-Swiveling Conformational antibody
Structural highlights
FunctionMMP14_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 PubMedMembrane 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
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