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==Crystal structure of the complex between MMP-8 and a non-zinc chelating inhibitor== | ==Crystal structure of the complex between MMP-8 and a non-zinc chelating inhibitor== | ||
<StructureSection load='3dpf' size='340' side='right' caption='[[3dpf]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='3dpf' size='340' side='right'caption='[[3dpf]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3dpf]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3dpf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DPF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AXB:N-{[2-(2-AMINO-3,4-DIOXOCYCLOBUT-1-EN-1-YL)-1,2,3,4-TETRAHYDROISOQUINOLIN-7-YL]METHYL}-4-OXO-3,5,6,8-TETRAHYDRO-4H-THIOPYRANO[4,3 4,5]THIENO[2,3-D]PYRIMIDINE-2-CARBOXAMIDE+7,7-DIOXIDE'>AXB</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=HAE:ACETOHYDROXAMIC+ACID'>HAE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AXB:N-{[2-(2-AMINO-3,4-DIOXOCYCLOBUT-1-EN-1-YL)-1,2,3,4-TETRAHYDROISOQUINOLIN-7-YL]METHYL}-4-OXO-3,5,6,8-TETRAHYDRO-4H-THIOPYRANO[4,3 4,5]THIENO[2,3-D]PYRIMIDINE-2-CARBOXAMIDE+7,7-DIOXIDE'>AXB</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=HAE:ACETOHYDROXAMIC+ACID'>HAE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3dpe|3dpe]], [[3dng|3dng]], [[1xuc|1xuc]], [[1xud|1xud]], [[1xur|1xur]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3dpe|3dpe]], [[3dng|3dng]], [[1xuc|1xuc]], [[1xud|1xud]], [[1xur|1xur]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMP8, CLG1 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MMP8, CLG1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Neutrophil_collagenase Neutrophil collagenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.34 3.4.24.34] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3dpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dpf OCA], [https://pdbe.org/3dpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dpf RCSB], [https://www.ebi.ac.uk/pdbsum/3dpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dpf ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/MMP8_HUMAN MMP8_HUMAN]] Can degrade fibrillar type I, II, and III collagens. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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</div> | </div> | ||
<div class="pdbe-citations 3dpf" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3dpf" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 36: | Line 39: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Neutrophil collagenase]] | [[Category: Neutrophil collagenase]] | ||
[[Category: Mazza, F]] | [[Category: Mazza, F]] | ||
Revision as of 11:04, 9 February 2022
Crystal structure of the complex between MMP-8 and a non-zinc chelating inhibitorCrystal structure of the complex between MMP-8 and a non-zinc chelating inhibitor
Structural highlights
Function[MMP8_HUMAN] Can degrade fibrillar type I, II, and III collagens. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe mode of binding and the activity of the first two non-zinc chelating, potent, and selective inhibitors of human neutrophil collagenase are reported. The crystal structures of the catalytic domain of MMP-8, respectively complexed with each inhibitor, reveals that both ligands are deeply inserted into the primary specificity subsite S(1)', where they induce a similar conformational change of the surrounding loop that is endowed with the main specificity determinants of MMPs. Accord to this rearrangement, both inhibitors remove the floor of the pocket formed by the Y227 side-chain, rendering available an extra binding region never explored before. The present data show that potent and more selective inhibitors can be obtained by developing ligands able to interact with the selectivity regions of the enzyme rather than with the catalytic zinc ion, which is the common feature of all MMP members. Extra Binding Region Induced by Non-Zinc Chelating Inhibitors into the S(1)' Subsite of Matrix Metalloproteinase 8 (MMP-8) (dagger).,Pochetti G, Montanari R, Gege C, Chevrier C, Taveras AG, Mazza F J Med Chem. 2009 Jan 27. PMID:19173605[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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