3o9h: Difference between revisions
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==Crystal Structure of wild-type HIV-1 Protease in complex with kd26== | |||
<StructureSection load='3o9h' size='340' side='right' caption='[[3o9h]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
{ | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3o9h]] is a 2 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=3O9H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O9H FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=K2E:(3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL+{(1S,2R)-3-[(1,3-BENZODIOXOL-5-YLSULFONYL)(2-ETHYLBUTYL)AMINO]-1-BENZYL-2-HYDROXYPROPYL}CARBAMATE'>K2E</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3o99|3o99]], [[3o9a|3o9a]], [[3o9b|3o9b]], [[3o9c|3o9c]], [[3o9d|3o9d]], [[3o9e|3o9e]], [[3o9f|3o9f]], [[3o9g|3o9g]], [[3o9i|3o9i]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gag-pol, 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=3o9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o9h OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o9h RCSB], [http://www.ebi.ac.uk/pdbsum/3o9h PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The rapid evolution of HIV under selective drug pressure has led to multidrug resistant (MDR) strains that evade standard therapies. We designed highly potent HIV-1 protease inhibitors (PIs) using the substrate envelope model, which confines inhibitors within the consensus volume of natural substrates, providing inhibitors less susceptible to resistance because a mutation affecting such inhibitors will simultaneously affect viral substrate processing. The designed PIs share a common chemical scaffold but utilize various moieties that optimally fill the substrate envelope, as confirmed by crystal structures. The designed PIs retain robust binding to MDR protease variants and display exceptional antiviral potencies against different clades of HIV as well as a panel of 12 drug-resistant viral strains. The substrate envelope model proves to be a powerful strategy to develop potent and robust inhibitors that avoid drug resistance. | |||
Substrate envelope-designed potent HIV-1 protease inhibitors to avoid drug resistance.,Nalam MN, Ali A, Reddy GS, Cao H, Anjum SG, Altman MD, Yilmaz NK, Tidor B, Rana TM, Schiffer CA Chem Biol. 2013 Sep 19;20(9):1116-24. doi: 10.1016/j.chembiol.2013.07.014. Epub, 2013 Sep 5. PMID:24012370<ref>PMID:24012370</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Virus protease|Virus protease]] | *[[Virus protease|Virus protease]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Nalam, M N.L | [[Category: Nalam, M N.L]] | ||
[[Category: Schiffer, C A | [[Category: Schiffer, C A]] | ||
[[Category: Aid]] | [[Category: Aid]] | ||
[[Category: Aspartyl protease]] | [[Category: Aspartyl protease]] | ||
Revision as of 01:50, 4 January 2015
Crystal Structure of wild-type HIV-1 Protease in complex with kd26Crystal Structure of wild-type HIV-1 Protease in complex with kd26
Structural highlights
Publication Abstract from PubMedThe rapid evolution of HIV under selective drug pressure has led to multidrug resistant (MDR) strains that evade standard therapies. We designed highly potent HIV-1 protease inhibitors (PIs) using the substrate envelope model, which confines inhibitors within the consensus volume of natural substrates, providing inhibitors less susceptible to resistance because a mutation affecting such inhibitors will simultaneously affect viral substrate processing. The designed PIs share a common chemical scaffold but utilize various moieties that optimally fill the substrate envelope, as confirmed by crystal structures. The designed PIs retain robust binding to MDR protease variants and display exceptional antiviral potencies against different clades of HIV as well as a panel of 12 drug-resistant viral strains. The substrate envelope model proves to be a powerful strategy to develop potent and robust inhibitors that avoid drug resistance. Substrate envelope-designed potent HIV-1 protease inhibitors to avoid drug resistance.,Nalam MN, Ali A, Reddy GS, Cao H, Anjum SG, Altman MD, Yilmaz NK, Tidor B, Rana TM, Schiffer CA Chem Biol. 2013 Sep 19;20(9):1116-24. doi: 10.1016/j.chembiol.2013.07.014. Epub, 2013 Sep 5. PMID:24012370[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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