3tsk: Difference between revisions
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[[ | ==Human MMP12 in complex with L-glutamate motif inhibitor== | ||
<StructureSection load='3tsk' size='340' side='right' caption='[[3tsk]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3tsk]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TSK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TSK FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=QEG:N~2~-{3-[4-(4-PHENYLTHIOPHEN-2-YL)PHENYL]PROPANOYL}-L-GLUTAMINYL-L-ALPHA-GLUTAMINE'>QEG</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">[[3ts4|3ts4]], [[3lik|3lik]], [[3lil|3lil]], [[3lir|3lir]], [[3ljg|3ljg]], [[3tt4|3tt4]], [[3tvc|3tvc]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HME, MMP12 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Macrophage_elastase Macrophage elastase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.65 3.4.24.65] </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=3tsk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tsk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tsk RCSB], [http://www.ebi.ac.uk/pdbsum/3tsk PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A series of pseudo-peptides with general formula X-l-Glu-NH(2) (with X corresponding to an acyl moiety with a long aryl-alkyl side chain) have been synthesized, evaluated as inhibitors of matrix metalloproteases (MMPs), and found to display remarkable nanomolar affinity. The loss in potency associated with a substitution of the P(2)' l-glutamate by a l-glutamine corroborates the importance of a carboxylate at this position. The binding mode of some of these inhibitors was characterized in solution and by x-ray crystallography in complex with various MMPs. The x-ray crystal structures reveal an unusual binding mode with the glutamate side chain chelating the active site zinc ion. Competition experiments between these inhibitors and acetohydroxamic acid, a small zinc-binding molecule, are in accord with the crystallographic results. One of these pseudo-dipeptides displays potency and selectivity toward MMP-12 similar to the best MMP-12 inhibitors reported to date. This novel family of pseudo peptides opens new opportunities to develop potent and selective inhibitors for several metzincins. | |||
Simple pseudo-dipeptides with a P2' glutamate: a novel inhibitor family of matrix metalloproteases and other metzincins.,Devel L, Beau F, Amoura M, Vera L, Cassar-Lajeunesse E, Garcia S, Czarny B, Stura EA, Dive V J Biol Chem. 2012 Aug 3;287(32):26647-56. Epub 2012 Jun 11. PMID:22689580<ref>PMID:22689580</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | |||
*[[Matrix metalloproteinase|Matrix metalloproteinase]] | |||
== | == References == | ||
[[ | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Macrophage elastase]] | [[Category: Macrophage elastase]] | ||
[[Category: Beau, F | [[Category: Beau, F]] | ||
[[Category: Czarny, B | [[Category: Czarny, B]] | ||
[[Category: Devel, L | [[Category: Devel, L]] | ||
[[Category: Dive, V | [[Category: Dive, V]] | ||
[[Category: Stura, E A | [[Category: Stura, E A]] | ||
[[Category: Vera, L | [[Category: Vera, L]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
[[Category: Metzincin]] | [[Category: Metzincin]] | ||
