View source for 8fuj


==HIV-1 wild type protease with GRL-03419A, with N-(2,5-dimethylphenyl)-4-(pyridin-3-yl)pyrimidin-2-amine as P2-P3 group and 3,5-difluorophenylmethyl as the P1 group==
<StructureSection load='8fuj' size='340' side='right'caption='[[8fuj]], [[Resolution|resolution]] 1.12&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8fuj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FUJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FUJ 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]] 1.12&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=Y9N:N-{(2S,3R)-1-(3,5-difluorophenyl)-3-hydroxy-4-[(4-methoxybenzene-1-sulfonyl)(2-methylpropyl)amino]butan-2-yl}-4-methyl-3-{[(4M)-4-(pyridin-3-yl)pyrimidin-2-yl]amino}benzamide'>Y9N</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=8fuj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fuj OCA], [https://pdbe.org/8fuj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fuj RCSB], [https://www.ebi.ac.uk/pdbsum/8fuj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fuj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q5RZ08_9HIV1 Q5RZ08_9HIV1] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Structure-based design, synthesis, X-ray structural studies, and biological evaluation of a new series of potent HIV-1 protease inhibitors are described. These inhibitors contain various pyridyl-pyrimidine, aryl thiazole or alkylthiazole derivatives as the P2 ligands in combination with darunavir-like hydroxyethylamine sulfonamide isosteres. These heterocyclic ligands are inherent to kinase inhibitor drugs, such as nilotinib and imatinib. These ligands are designed to make hydrogen bonding interactions with the backbone atoms in the S2 subsite of HIV-1 protease. Various benzoic acid derivatives have been synthesized and incorporation of these ligands provided potent inhibitors that exhibited subnanomolar level protease inhibitory activity and low nanomolar level antiviral activity. Two high resolution X-ray structures of inhibitor-bound HIV-1 protease were determined. These structures provided important ligand-binding site interactions for further optimization of this class of protease inhibitors.

Exploration of imatinib and nilotinib-derived templates as the P2-Ligand for HIV-1 protease inhibitors: Design, synthesis, protein X-ray structural studies, and biological evaluation.,Ghosh AK, Mishevich JL, Kovela S, Shaktah R, Ghosh AK, Johnson M, Wang YF, Wong-Sam A, Agniswamy J, Amano M, Takamatsu Y, Hattori SI, Weber IT, Mitsuya H Eur J Med Chem. 2023 Jul 5;255:115385. doi: 10.1016/j.ejmech.2023.115385. Epub , 2023 Apr 21. PMID:37150084<ref>PMID:37150084</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8fuj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Agniswamy J]]
[[Category: Ghosh AK]]
[[Category: Wang Y-F]]
[[Category: Weber IT]]