2f7d: Difference between revisions
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==A mutant rabbit cathepsin K with a nitrile inhibitor== | ==A mutant rabbit cathepsin K with a nitrile inhibitor== | ||
<StructureSection load='2f7d' size='340' side='right' caption='[[2f7d]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='2f7d' size='340' side='right' caption='[[2f7d]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTSK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTSK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_K Cathepsin K], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.38 3.4.22.38] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_K Cathepsin K], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.38 3.4.22.38] </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=2f7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f7d OCA], [http://pdbe.org/2f7d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2f7d RCSB], [http://www.ebi.ac.uk/pdbsum/2f7d PDBsum]</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=2f7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f7d OCA], [http://pdbe.org/2f7d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2f7d RCSB], [http://www.ebi.ac.uk/pdbsum/2f7d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2f7d ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 2f7d" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 2f7d" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 10:34, 18 October 2017
A mutant rabbit cathepsin K with a nitrile inhibitorA mutant rabbit cathepsin K with a nitrile inhibitor
Structural highlights
Function[CATK_RABIT] Closely involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation. 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 PubMedA new series of nonpeptidic cathepsin K inhibitors that are based on a beta-substituted cyclohexanecarboxamide motif has been developed. Lead optimization yielded compounds with sub-nanomolar potency and exceptional selectivity profiles against cathepsins B, L, and S. Use of fluorine atoms to block metabolism on the cyclohexyl ring led to compounds with excellent pharmacokinetic properties. Considering the well-established role of cathepsin K in osteoclast-mediated bone turnover, compounds such as (-)-34a (hrab Cat K IC(50) 0.28 nM; >800-fold selectivity vs Cat B, L, and S; PK data in dogs: F 55%, t(1/2) = 15 h) exhibit great potential for development as an orally bioavailable therapeutic for treatment of diseases that involve bone loss. Beta-substituted cyclohexanecarboxamide: a nonpeptidic framework for the design of potent inhibitors of cathepsin K.,Crane SN, Black WC, Palmer JT, Davis DE, Setti E, Robichaud J, Paquet J, Oballa RM, Bayly CI, McKay DJ, Somoza JR, Chauret N, Seto C, Scheigetz J, Wesolowski G, Masse F, Desmarais S, Ouellet M J Med Chem. 2006 Feb 9;49(3):1066-79. PMID:16451072[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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