3ogq: Difference between revisions
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[[ | ==Crystal Structure of 6s-98S FIV Protease with Lopinavir bound== | ||
<StructureSection load='3ogq' size='340' side='right' caption='[[3ogq]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3ogq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Feline_immunodeficiency_virus Feline immunodeficiency virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OGQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3OGQ FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AB1:N-{1-BENZYL-4-[2-(2,6-DIMETHYL-PHENOXY)-ACETYLAMINO]-3-HYDROXY-5-PHENYL-PENTYL}-3-METHYL-2-(2-OXO-TETRAHYDRO-PYRIMIDIN-1-YL)-BUTYRAMIDE'>AB1</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1b11|1b11]], [[2hah|2hah]], [[3ogp|3ogp]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pol, PR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11673 Feline immunodeficiency virus])</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=3ogq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ogq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ogq RCSB], [http://www.ebi.ac.uk/pdbsum/3ogq PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A chimeric feline immunodeficiency virus (FIV) protease (PR) has been engineered that supports infectivity but confers sensitivity to the human immunodeficiency virus (HIV) PR inhibitors darunavir (DRV) and lopinavir (LPV). The 6s-98S PR has five replacements mimicking homologous residues in HIV PR and a sixth which mutated from Pro to Ser during selection. Crystal structures of the 6s-98S FIV PR chimera with DRV and LPV bound have been determined at 1.7 and 1.8 A resolution, respectively. The structures reveal the role of a flexible 90s loop and residue 98 in supporting Gag processing and infectivity and the roles of residue 37 in the active site and residues 55, 57 and 59 in the flap in conferring the ability to specifically recognize HIV PR drugs. Specifically, Ile37Val preserves tertiary structure but prevents steric clashes with DRV and LPV. Asn55Met and Val59Ile induce a distinct kink in the flap and a new hydrogen bond to DRV. Ile98Pro-->Ser and Pro100Asn increase 90s loop flexibility, Gln99Val contributes hydrophobic contacts to DRV and LPV, and Pro100Asn forms compensatory hydrogen bonds. The chimeric PR exhibits a comparable number of hydrogen bonds, electrostatic interactions and hydrophobic contacts with DRV and LPV as in the corresponding HIV PR complexes, consistent with IC(50) values in the nanomolar range. | |||
Structural basis for drug and substrate specificity exhibited by FIV encoding a chimeric FIV/HIV protease.,Lin YC, Perryman AL, Olson AJ, Torbett BE, Elder JH, Stout CD Acta Crystallogr D Biol Crystallogr. 2011 Jun;67(Pt 6):540-8. Epub 2011 May 12. PMID:21636894<ref>PMID:21636894</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: Feline immunodeficiency virus]] | [[Category: Feline immunodeficiency virus]] | ||
[[Category: Elder, J H | [[Category: Elder, J H]] | ||
[[Category: Lin, Y C | [[Category: Lin, Y C]] | ||
[[Category: Perryman, A L | [[Category: Perryman, A L]] | ||
[[Category: Stout, C D | [[Category: Stout, C D]] | ||
[[Category: Aspartyl protease]] | [[Category: Aspartyl protease]] | ||
[[Category: Hiv-like fiv chimera]] | [[Category: Hiv-like fiv chimera]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
Revision as of 14:45, 9 December 2014
Structural highlights
Publication Abstract from PubMedA chimeric feline immunodeficiency virus (FIV) protease (PR) has been engineered that supports infectivity but confers sensitivity to the human immunodeficiency virus (HIV) PR inhibitors darunavir (DRV) and lopinavir (LPV). The 6s-98S PR has five replacements mimicking homologous residues in HIV PR and a sixth which mutated from Pro to Ser during selection. Crystal structures of the 6s-98S FIV PR chimera with DRV and LPV bound have been determined at 1.7 and 1.8 A resolution, respectively. The structures reveal the role of a flexible 90s loop and residue 98 in supporting Gag processing and infectivity and the roles of residue 37 in the active site and residues 55, 57 and 59 in the flap in conferring the ability to specifically recognize HIV PR drugs. Specifically, Ile37Val preserves tertiary structure but prevents steric clashes with DRV and LPV. Asn55Met and Val59Ile induce a distinct kink in the flap and a new hydrogen bond to DRV. Ile98Pro-->Ser and Pro100Asn increase 90s loop flexibility, Gln99Val contributes hydrophobic contacts to DRV and LPV, and Pro100Asn forms compensatory hydrogen bonds. The chimeric PR exhibits a comparable number of hydrogen bonds, electrostatic interactions and hydrophobic contacts with DRV and LPV as in the corresponding HIV PR complexes, consistent with IC(50) values in the nanomolar range. Structural basis for drug and substrate specificity exhibited by FIV encoding a chimeric FIV/HIV protease.,Lin YC, Perryman AL, Olson AJ, Torbett BE, Elder JH, Stout CD Acta Crystallogr D Biol Crystallogr. 2011 Jun;67(Pt 6):540-8. Epub 2011 May 12. PMID:21636894[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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