View source for 4fae


==Substrate p2/NC in Complex with a Human Immunodeficiency Virus Type 1 Protease Variant==
<StructureSection load='4fae' size='340' side='right'caption='[[4fae]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</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>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q000H7_9HIV1 Q000H7_9HIV1] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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>
<div class="pdbe-citations 4fae" style="background-color:#fffaf0;"></div>

==See Also==
*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Brunzelle JS]]
[[Category: Dewdney TG]]
[[Category: Kovari IA]]
[[Category: Kovari LC]]
[[Category: Liu Z]]
[[Category: Reiter SJ]]
[[Category: Wang Y]]