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5hct
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Endothiapepsin in complex with biacylhydrazone== | |
| + | <StructureSection load='5hct' size='340' side='right' caption='[[5hct]], [[Resolution|resolution]] 1.36Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5hct]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HCT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HCT FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=61P:2-AMINO-N-{3-[(E)-{2-[(2S)-2-AMINO-3-(1H-INDOL-3-YL)PROPANOYL]HYDRAZINYLIDENE}METHYL]BENZYLIDENE}-3-(1H-INDOL-2-YL)PROPANEHYDRAZIDE+(NON-PREFERRED+NAME)'>61P</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pgi|3pgi]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Endothiapepsin Endothiapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.22 3.4.23.22] </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=5hct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hct OCA], [http://pdbe.org/5hct PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hct RCSB], [http://www.ebi.ac.uk/pdbsum/5hct PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hct ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Fragment-based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit-identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X-ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis-acylhydrazones and used DCC to identify potent inhibitors. The most potent inhibitor exhibits an IC50 value of 54 nm, which represents a 240-fold improvement in potency compared to the parent hits. Subsequent X-ray crystallography validated the predicted binding mode, thus demonstrating the efficiency of the combination of fragment linking and DCC as a hit-identification strategy. This approach could be applied to a range of biological targets, and holds the potential to facilitate hit-to-lead optimization. | ||
| - | + | Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry.,Mondal M, Radeva N, Fanlo-Virgos H, Otto S, Klebe G, Hirsch AK Angew Chem Int Ed Engl. 2016 Jul 12. doi: 10.1002/anie.201603074. PMID:27400756<ref>PMID:27400756</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5hct" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Cryphonectria parasitica]] | ||
| + | [[Category: Endothiapepsin]] | ||
[[Category: Heine, A]] | [[Category: Heine, A]] | ||
| + | [[Category: Klebe, G]] | ||
[[Category: Radeva, N]] | [[Category: Radeva, N]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Inhibition]] | ||
Revision as of 15:19, 26 July 2016
Endothiapepsin in complex with biacylhydrazone
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