View source for 5hct


==Endothiapepsin in complex with biacylhydrazone==
<StructureSection load='5hct' size='340' side='right'caption='[[5hct]], [[Resolution|resolution]] 1.36&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5hct]] is a 1 chain structure with sequence from [https://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 [https://proteopedia.org/fgij/fg.htm?mol=5HCT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.36&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5hct FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hct OCA], [https://pdbe.org/5hct PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hct RCSB], [https://www.ebi.ac.uk/pdbsum/5hct PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hct ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CARP_CRYPA CARP_CRYPA] 
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5hct" style="background-color:#fffaf0;"></div>

==See Also==
*[[Pepsin|Pepsin]]
== References ==
<references/>
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</StructureSection>
[[Category: Cryphonectria parasitica]]
[[Category: Large Structures]]
[[Category: Heine A]]
[[Category: Klebe G]]
[[Category: Radeva N]]