4gye: Difference between revisions
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==MDR 769 HIV-1 Protease in Complex with Reduced P1F== | ==MDR 769 HIV-1 Protease in Complex with Reduced P1F== | ||
<StructureSection load='4gye' size='340' side='right' caption='[[4gye]], [[Resolution|resolution]] 2.27Å' scene=''> | <StructureSection load='4gye' size='340' side='right'caption='[[4gye]], [[Resolution|resolution]] 2.27Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4gye]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4gye]] 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=4GYE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GYE FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ILO:N5-IMINOETHYL-L-ORNITHINE'>ILO</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene>, <scene name='pdbligand=PUK:N-[(2S)-2-AMINO-3-PHENYLPROPYL]-L-PHENYLALANINE'>PUK</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=4gye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gye OCA], [https://pdbe.org/4gye PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gye RCSB], [https://www.ebi.ac.uk/pdbsum/4gye PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gye ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9QM22_9HIV1 Q9QM22_9HIV1] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 4gye" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4gye" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Brunzelle | [[Category: Large Structures]] | ||
[[Category: Dewdney | [[Category: Brunzelle J]] | ||
[[Category: Kovari | [[Category: Dewdney TG]] | ||
[[Category: Kovari | [[Category: Kovari IA]] | ||
[[Category: Reiter | [[Category: Kovari LC]] | ||
[[Category: Wang | [[Category: Reiter SJ]] | ||
[[Category: Wang Y]] | |||
Revision as of 10:26, 26 October 2022
MDR 769 HIV-1 Protease in Complex with Reduced P1FMDR 769 HIV-1 Protease in Complex with Reduced P1F
Structural highlights
FunctionPublication Abstract from PubMedProper proteolytic processing of the HIV-1 Gag/Pol polyprotein is required for HIV infection and viral replication. This feature has made HIV-1 protease an attractive target for antiretroviral drug design for the treatment of HIV-1 infected patients. To examine the role of the P1 and P1'positions of the substrate in inhibitory efficacy of multi-drug resistant HIV-1 protease 769 (MDR 769), we performed a series of structure-function studies. Using the original CA/p2 cleavage site sequence, we generated heptapeptides containing one reduced peptide bond with an L to F and A to F double mutation at P1 and P1' (F-r-F), and an A to F at P1' (L-r-F) resulting in P1/P1' modified ligands. Here, we present an analysis of co-crystal structures of CA/p2 F-r-F, and CA/p2 L-r-F in complex with MDR 769. To examine conformational changes in the complex structure, molecular dynamic (MD) simulations were performed with MDR769-ligand complexes. MD trajectories show the isobutyl group of both the lopinavir analog and the CA/p2 L-r-F substrate cause a conformational change of in the active site of MDR 769. IC50 measurements suggest the non identical P1/P1' ligands (CA/p2 L-r-F and lopinavir analog) are more effective against MDR proteases as opposed to identical P1/P1'ligands. Our results suggest that a non identical P1/P1'composition may be more favorable for the inhibition of MDR 769 as they induce conformational changes in the active site of the enzyme resulting in disruption of the two-fold symmetry of the protease, thus, stabilizing the inhibitor in the active site. Ligand modifications to reduce the relative resistance of multi-drug resistant HIV-1 protease.,Dewdney TG, Wang Y, Liu Z, Sharma SK, Reiter SJ, Brunzelle JS, Kovari IA, Woster PM, Kovari LC Bioorg Med Chem. 2013 Sep 27. pii: S0968-0896(13)00825-0. doi:, 10.1016/j.bmc.2013.09.045. PMID:24128815[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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