4fae: Difference between revisions

<table><tr><td colspan='2'>[[4fae]] is a 3 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=4FAE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FAE FirstGlance]. <br>

</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=4fae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fae OCA], [https://pdbe.org/4fae PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fae RCSB], [https://www.ebi.ac.uk/pdbsum/4fae PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fae ProSAT]</span></td></tr>

[https://www.uniprot.org/uniprot/Q000H7_9HIV1 Q000H7_9HIV1]  

Designing HIV-1 protease inhibitors that overcome drug-resistance is still a challenging task. In this study, four clinical isolates of multi-drug resistant HIV-1 proteases that exhibit resistance to all the US FDA-approved HIV-1 protease inhibitors and also reduce the substrate recognition ability were examined. A multi-drug resistant HIV-1 protease isolate, MDR 769, was co-crystallized with the p2/NC substrate and the mutated CA/p2 substrate, CA/p2 P1'F. Both substrates display different levels of molecular recognition by the wild-type and multi-drug resistant HIV-1 protease. From the crystal structures, only limited differences can be identified between the wild-type and multi-drug resistant protease. Therefore, a wild-type HIV-1 protease and four multi-drug resistant HIV-1 proteases in complex with the two peptides were modeled based on the crystal structures and examined during a 10 ns-molecular dynamics simulation. The simulation results reveal that the multi-drug resistant HIV-1 proteases require higher desolvation energy to form complexes with the peptides. This result suggests that the desolvation of the HIV-1 protease active site is an important step of protease-ligand complex formation as well as drug resistance. Therefore, desolvation energy could be considered as a parameter in the evaluation of future HIV-1 protease inhibitor candidates.

 

Higher Desolvation Energy Reduces Molecular Recognition in Multi-Drug Resistant HIV-1 Protease.,Wang Y, Dewdney TG, Liu Z, Reiter SJ, Brunzelle JS, Kovari IA, Kovari LC Biology (Basel). 2012 May 31;1(1):81-93. doi: 10.3390/biology1010081. PMID:24832048<ref>PMID:24832048</ref>

 

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

<div class="pdbe-citations 4fae" style="background-color:#fffaf0;"></div>

[[Category: Human immunodeficiency virus 1]]

[[Category: Brunzelle JS]]

[[Category: Dewdney TG]]

[[Category: Kovari IA]]

[[Category: Kovari LC]]

[[Category: Liu Z]]

[[Category: Reiter SJ]]

[[Category: Wang Y]]