View source for 7wcq


==Crystal structure of HIV-1 protease in complex with lactam derivative 1==
<StructureSection load='7wcq' size='340' side='right'caption='[[7wcq]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7wcq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus Human immunodeficiency virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WCQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WCQ 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]] 2.011&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8OC:(3R,4R)-3-[(4-fluorophenyl)methyl]-1-[(4-methoxyphenyl)methyl]-3-(4-methylsulfonylphenyl)-4-oxidanyl-pyrrolidin-2-one'>8OC</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=7wcq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wcq OCA], [https://pdbe.org/7wcq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wcq RCSB], [https://www.ebi.ac.uk/pdbsum/7wcq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wcq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9WFL7_9HIV1 Q9WFL7_9HIV1] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A novel strategy for lead identification that we have dubbed the "Pocket-to-Lead" strategy is demonstrated using HIV-1 protease as a model target. Sometimes, it is difficult to obtain hit compounds because of the difficulties in satisfying the complex pharmacophoric features. In this study, a virtual fragment hit which does not match all of the pharmacophore features but has key interactions and vectors that could grow into remaining pharmacophore features was optimized in silico. The designed compound 9 demonstrated weak but evident inhibitory activity (IC50 = 54 muM), and the design concept was proven by the co-crystal structure. Then, structure-based drug design promptly gave compound 14 (IC50 = 0.0071 muM, EC50 = 0.86 muM), an almost 10,000-fold improvement in activity from 9. The structure of the designed molecules proved to be novel with high synthetic feasibility, indicating the usefulness of this strategy to tackle tough targets with complex pharmacophore.

Pocket-to-Lead: Structure-Based De Novo Design of Novel Non-peptidic HIV-1 Protease Inhibitors Using the Ligand Binding Pocket as a Template.,Kojima E, Iimuro A, Nakajima M, Kinuta H, Asada N, Sako Y, Nakata Z, Uemura K, Arita S, Miki S, Wakasa-Morimoto C, Tachibana Y J Med Chem. 2022 Apr 28;65(8):6157-6170. doi: 10.1021/acs.jmedchem.1c02217. Epub , 2022 Apr 13. PMID:35416651<ref>PMID:35416651</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7wcq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human immunodeficiency virus]]
[[Category: Large Structures]]
[[Category: Arita S]]
[[Category: Asada N]]
[[Category: Fumoto M]]
[[Category: Iimuro A]]
[[Category: Kinuta H]]
[[Category: Kojima E]]
[[Category: Miki S]]
[[Category: Nakajima M]]
[[Category: Nakata Z]]
[[Category: Sako Y]]
[[Category: Tachibana Y]]
[[Category: Uemura K]]
[[Category: Wakasa-Morimoto C]]