View source for 4auo


==Crystal structure of MMP-1(E200A) in complex with a triple-helical collagen peptide==
<StructureSection load='4auo' size='340' side='right'caption='[[4auo]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4auo]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AUO 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]] 3&#8491;</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=HYP:4-HYDROXYPROLINE'>HYP</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=4auo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4auo OCA], [https://pdbe.org/4auo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4auo RCSB], [https://www.ebi.ac.uk/pdbsum/4auo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4auo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MMP1_HUMAN MMP1_HUMAN] Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X. In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity.<ref>PMID:1645757</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Collagenases of the matrix metalloproteinase (MMP) family play major roles in morphogenesis, tissue repair, and human diseases, but how they recognize and cleave the collagen triple helix is not fully understood. Here, we report temperature-dependent binding of a catalytically inactive MMP-1 mutant (E200A) to collagen through the cooperative action of its catalytic and hemopexin domains. Contact between the two molecules was mapped by screening the Collagen Toolkit peptide library and by hydrogen/deuterium exchange. The crystal structure of MMP-1(E200A) bound to a triple-helical collagen peptide revealed extensive interactions of the 115-A-long triple helix with both MMP-1 domains. An exosite in the hemopexin domain, which binds the leucine 10 residues C-terminal to the scissile bond, is critical for collagenolysis and represents a unique target for inhibitor development. The scissile bond is not correctly positioned for hydrolysis in the crystallized complex. A productive binding mode is readily modeled, without altering the MMP-1 structure or the exosite interactions, by axial rotation of the collagen homotrimer. Interdomain flexing of the enzyme and a localized excursion of the collagen chain closest to the active site, facilitated by thermal loosening of the substrate, may lead to the first transition state of collagenolysis.

Structural insights into triple-helical collagen cleavage by matrix metalloproteinase 1.,Manka SW, Carafoli F, Visse R, Bihan D, Raynal N, Farndale RW, Murphy G, Enghild JJ, Hohenester E, Nagase H Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12461-6. Epub 2012 Jul 3. PMID:22761315<ref>PMID:22761315</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4auo" 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: Synthetic construct]]
[[Category: Bihan D]]
[[Category: Carafoli F]]
[[Category: Enghild JJ]]
[[Category: Farndale RW]]
[[Category: Hohenester E]]
[[Category: Manka SW]]
[[Category: Murphy G]]
[[Category: Nagase H]]
[[Category: Raynal N]]
[[Category: Visse R]]