3ogq

Crystal Structure of 6s-98S FIV Protease with Lopinavir bound

spinqualitylabelsall models 3ogq, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ogq is a 2 chain structure with sequence from Feline immunodeficiency virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: AB1, DMS Related: 1b11, 2hah, 3ogp Gene: pol, PR (Feline immunodeficiency virus) Resources: FirstGlance, OCA, RCSB, PDBsum Function [POL_FIVPE] During replicative cycle of retroviruses, the reverse-transcribed viral DNA is integrated into the host chromosome by the viral integrase enzyme. RNase H activity is associated with the reverse transcriptase. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Virus protease

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