4mzs: Difference between revisions

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-'''Unreleased structure'''
+==Mouse cathepsin s with covalent ligand (3S,4S)-1-[(2-CHLOROPHENYL)SULFONYL]-N-[(2E)-2-IMINOETHYL]-4-(MORPHOLIN-4-YLCARBONYL)PYRROLIDINE-3-CARBOXAMIDE==
+<StructureSection load='4mzs' size='340' side='right' caption='[[4mzs]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4mzs]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MZS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MZS FirstGlance]. <br>
+</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2EV:(3S,4S)-1-[(2-CHLOROPHENYL)SULFONYL]-N-[(2E)-2-IMINOETHYL]-4-(MORPHOLIN-4-YLCARBONYL)PYRROLIDINE-3-CARBOXAMIDE'>2EV</scene><br>
+<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4bsq|4bsq]], [[4bs5|4bs5]], [[4mzo|4mzo]]</td></tr>
+<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mzs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mzs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mzs RCSB], [http://www.ebi.ac.uk/pdbsum/4mzs PDBsum]</span></td></tr>
+<table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Starting from the weakly active dual CatS/K inhibitor 5, structure-based design supported by X-ray analysis led to the discovery of the potent and selective (&gt;50 000-fold vs CatK) cyclopentane derivative 22 by exploiting specific ligand-receptor interactions in the S2 pocket of CatS. Changing the central cyclopentane scaffold to the analogous pyrrolidine derivative 57 decreased the enzyme as well as the cell-based activity significantly by 24- and 69-fold, respectively. The most promising scaffold identified was the readily accessible proline derivative (e.g., 79). This compound, with an appealing ligand efficiency (LE) of 0.47, included additional structural modifications binding in the S1 and S3 pockets of CatS, leading to favorable in vitro and in vivo properties. Compound 79 reduced IL-2 production in a transgenic DO10.11 mouse model of antigen presentation in a dose-dependent manner with an ED50 of 5 mg/kg.
-The entry 4mzs is ON HOLD  until Paper Publication
+Identification of Potent and Selective Cathepsin S Inhibitors Containing Different Central Cyclic Scaffolds.,Hilpert H, Mauser H, Humm R, Anselm L, Kuehne H, Hartmann G, Gruener S, Banner DW, Benz J, Gsell B, Kuglstatter A, Stihle M, Thoma R, Sanchez RA, Iding H, Wirz B, Haap W J Med Chem. 2013 Nov 22. PMID:24224654<ref>PMID:24224654</ref>
-Authors: Kuglstatter, A., Stihle, M.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description:
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Cathepsin S]]
+[[Category: Kuglstatter, A.]]
+[[Category: Stihle, M.]]
+[[Category: Cysteine protease]]
+[[Category: Hydrolase]]
+[[Category: Hydrolase-hydrolase inhibitor complex]]