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4qxu

From Proteopedia

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

Structural highlights

4qxu is a 3 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4qxu"

@@ Line 1: / Line 1: @@
 ==Novel Inhibition Mechanism of Membrane Metalloprotease by an Exosite-Swiveling Conformational antibody==
-<StructureSection load='4qxu' size='340' side='right' caption='[[4qxu]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+<StructureSection load='4qxu' size='340' side='right'caption='[[4qxu]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4qxu]] is a 3 chain structure. 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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</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='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='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'>[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='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://www.rcsb.org/pdb/explore.do?structureId=4qxu RCSB], [http://www.ebi.ac.uk/pdbsum/4qxu PDBsum]</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&reg;/PubMed&reg;, 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: Membrane-type matrix metalloproteinase-1]]
+[[Category: Homo sapiens]]
-[[Category: Arroyo, A G]]
+[[Category: Large Structures]]
-[[Category: Cuiniasse, P]]
+[[Category: Mus musculus]]
-[[Category: Dive, V]]
+[[Category: Arroyo AG]]
-[[Category: Dym, O]]
+[[Category: Cuiniasse P]]
-[[Category: Grossman, M]]
+[[Category: Dive V]]
-[[Category: ISPC, Israel Structural Proteomics Center]]
+[[Category: Dym O]]
-[[Category: Moreno, v]]
+[[Category: Grossman M]]
-[[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: Igg fold]]
+[[Category: Udi Y]]
-[[Category: Immune system]]
-[[Category: PSI, Protein structure initiative]]
-[[Category: Structural genomic]]

4qxu

From Proteopedia

Current revision

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

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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