View source for 3wz6


==Endothiapepsin in complex with Gewald reaction-derived inhibitor (5)==
<StructureSection load='3wz6' size='340' side='right' caption='[[3wz6]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3wz6]] 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=3WZ6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WZ6 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=IXZ:N-BENZYL-2-[(N-BENZYLGLYCYL)AMINO]-4-PHENYLTHIOPHENE-3-CARBOXAMIDE'>IXZ</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PG6:1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE'>PG6</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3wz7|3wz7]], [[3wz8|3wz8]]</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=3wz6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wz6 OCA], [http://pdbe.org/3wz6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wz6 RCSB], [http://www.ebi.ac.uk/pdbsum/3wz6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wz6 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Successful lead optimization in structure-based drug discovery depends on the correct deduction and interpretation of the underlying structure-activity relationships (SAR) to facilitate efficient decision-making on the next candidates to be synthesized. Consequently, the question arises, how frequently a binding mode (re)-validation is required, to ensure not to be misled by invalid assumptions on the binding geometry. We present an example in which minor chemical modifications within one inhibitor series lead to surprisingly different binding modes. X-ray structure determination of eight inhibitors derived from one core scaffold resulted in four different binding modes in the aspartic protease endothiapepsin, a well-established surrogate for e.g. renin and beta-secretase. In addition, we suggest an empirical metrics that might serve as an indicator during lead optimization to qualify compounds as candidates for structural revalidation.

Tracing binding modes in hit-to-lead optimization: chameleon-like poses of aspartic protease inhibitors.,Kuhnert M, Koster H, Bartholomaus R, Park AY, Shahim A, Heine A, Steuber H, Klebe G, Diederich WE Angew Chem Int Ed Engl. 2015 Feb 23;54(9):2849-53. doi: 10.1002/anie.201411206., Epub 2015 Jan 28. PMID:25630461<ref>PMID:25630461</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3wz6" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Cryphonectria parasitica]]
[[Category: Endothiapepsin]]
[[Category: Diederich, W E]]
[[Category: Kuhnert, M]]
[[Category: Steuber, H]]
[[Category: Aspartic protease]]
[[Category: Hydrolase-hydrolase inhibitor complex]]