View source for 4z50


==Crystal Structure of Multidrug Resistant HIV-1 Protease Clinical Isolate PR20D25N with Tucked Flap==
<StructureSection load='4z50' size='340' side='right' caption='[[4z50]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4z50]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z50 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z50 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4z4x|4z4x]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</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=4z50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z50 OCA], [http://pdbe.org/4z50 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z50 RCSB], [http://www.ebi.ac.uk/pdbsum/4z50 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4z50 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Molecular mechanisms leading to high level drug resistance have been analyzed for the clinical variant of HIV-1 protease bearing 20 mutations (PR20); which has several orders of magnitude worse affinity for tested drugs. Two crystal structures of ligand-free PR20 with the D25N mutation of the catalytic aspartate (PR20D25N) revealed three dimers with different flap conformations. The diverse conformations of PR20D25N included a dimer with one flap in a unique "tucked" conformation; directed into the active site. Analysis of molecular dynamics (MD) simulations of the ligand-free PR20 and wild-type enzymes showed that the mutations in PR20 alter the correlated interactions between two monomers in the dimer. The two flaps tend to fluctuate more independently in PR20 than in the wild type enzyme. Combining the results of structural analysis by X-ray crystallography and MD simulations; unusual flap conformations and weakly correlated inter-subunit motions may contribute to the high level resistance of PR20.

Conformational variation of an extreme drug resistant mutant of HIV protease.,Shen CH, Chang YC, Agniswamy J, Harrison RW, Weber IT J Mol Graph Model. 2015 Sep 8;62:87-96. doi: 10.1016/j.jmgm.2015.09.006. PMID:26397743<ref>PMID:26397743</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4z50" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Agniswamy, J]]
[[Category: Shen, C H]]
[[Category: Weber, I T]]
[[Category: Hiv-1 protease]]
[[Category: Hydrolase]]