4p6e: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
Line 1: Line 1:
'''Unreleased structure'''
==Crystal Structure of Human Cathepsin S Bound to a Non-covalent Inhibitor==
<StructureSection load='4p6e' size='340' side='right' caption='[[4p6e]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4p6e]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P6E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P6E FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2FC:N-[(8R)-8-(BENZOYLAMINO)-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL]-4-METHYLPIPERAZINE-1-CARBOXAMIDE'>2FC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_S Cathepsin S], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.27 3.4.22.27] </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=4p6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p6e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p6e RCSB], [http://www.ebi.ac.uk/pdbsum/4p6e PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cathepsin S (Cat S) plays an important role in many pathological conditions, including abdominal aortic aneurysm (AAA). Inhibition of Cat S may provide a new treatment for AAA. To date, several classes of Cat S inhibitors have been reported, many of which form covalent interactions with the active site Cys25. Herein, we report the discovery of a novel series of noncovalent inhibitors of Cat S through a medium-throughput focused cassette screen and the optimization of the resulting hits. Structure-based optimization efforts led to Cat S inhibitors such as 5 and 9 with greatly improved potency and drug disposition properties. This series of compounds binds to the S2 and S3 subsites without interacting with the active site Cys25. On the basis of in vitro potency, selectivity, and efficacy in a CaCl2-induced AAA in vivo model, 5 (LY3000328) was selected for clinical development.


The entry 4p6e is ON HOLD  until Paper Publication
Discovery of Cathepsin S Inhibitor LY3000328 for the Treatment of Abdominal Aortic Aneurysm.,Jadhav PK, Schiffler MA, Gavardinas K, Kim EJ, Matthews DP, Staszak MA, Coffey DS, Shaw BW, Cassidy KC, Brier RA, Zhang Y, Christie RM, Matter WF, Qing K, Durbin JD, Wang Y, Deng GG ACS Med Chem Lett. 2014 Aug 27;5(10):1138-42. doi: 10.1021/ml500283g. eCollection, 2014 Oct 9. PMID:25313327<ref>PMID:25313327</ref>


Authors: Wang, Y., Jadhav, P.K., Deng, G.G.
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
Description: Crystal Structure of Human Cathepsin S Bound to a Non-covalent Inhibitor
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Cathepsin S]]
[[Category: Deng, G G.]]
[[Category: Jadhav, P K.]]
[[Category: Wang, Y.]]
[[Category: Cathepsin s]]
[[Category: Cysteine protease]]
[[Category: Inhibitor]]
[[Category: Non-covalent]]
Retrieved from "https://proteopedia.org/4p6e"