3v96: Difference between revisions
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==Complex of matrix metalloproteinase-10 catalytic domain (MMP-10cd) with tissue inhibitor of metalloproteinases-1 (TIMP-1)== | |||
<StructureSection load='3v96' size='340' side='right'caption='[[3v96]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3v96]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3V96 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V96 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]] 1.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3v96 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v96 OCA], [https://pdbe.org/3v96 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v96 RCSB], [https://www.ebi.ac.uk/pdbsum/3v96 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v96 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TIMP1_HUMAN TIMP1_HUMAN] Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Also mediates erythropoiesis in vitro; but, unlike IL-3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-12, MMP-13 and MMP-16. Does not act on MMP-14. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Matrix metalloproteinase 10 (MMP-10, stromelysin-2) is a secreted metalloproteinase with functions in skeletal development, wound healing, and vascular remodeling; its overexpression is also implicated in lung tumorigenesis and tumor progression. To understand the regulation of MMP-10 by tissue inhibitors of metalloproteinases (TIMPs), we have assessed equilibrium inhibition constants (K(i)) of putative physiological inhibitors TIMP-1 and TIMP-2 for the active catalytic domain of human MMP-10 (MMP-10cd) using multiple kinetic approaches. We find that TIMP-1 inhibits the MMP-10cd with a K(i) of 1.1 x 10(-9) M; this interaction is 10-fold weaker than the inhibition of the similar MMP-3 (stromelysin-1) catalytic domain (MMP-3cd) by TIMP-1. TIMP-2 inhibits the MMP-10cd with a K(i) of 5.8 x 10(-9) M, which is again 10-fold weaker than the inhibition of MMP-3cd by this inhibitor (K(i) = 5.5 x 10(-10) M). We solved the x-ray crystal structure of TIMP-1 bound to the MMP-10cd at 1.9 A resolution; the structure was solved by molecular replacement and refined with an R-factor of 0.215 (R(free) = 0.266). Comparing our structure of MMP-10cd.TIMP-1 with the previously solved structure of MMP-3cd.TIMP-1 (Protein Data Bank entry 1UEA), we see substantial differences at the binding interface that provide insight into the differential binding of stromelysin family members to TIMP-1. This structural information may ultimately assist in the design of more selective TIMP-based inhibitors tailored for specificity toward individual members of the stromelysin family, with potential therapeutic applications. | |||
Matrix metalloproteinase-10 (MMP-10) interaction with tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2: binding studies and crystal structure.,Batra J, Robinson J, Soares AS, Fields AP, Radisky DC, Radisky ES J Biol Chem. 2012 May 4;287(19):15935-46. Epub 2012 Mar 16. PMID:22427646<ref>PMID:22427646</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3v96" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Batra J]] | |||
[[Category: Radisky ES]] | |||
[[Category: Soares AS]] | |||
