5tys

X-ray crystal structure of wild type HIV-1 protease in complex with GRL-142

spinqualitylabelsall models 5tys, resolution 2.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5tys is a 2 chain structure with sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.007Å Ligands: 7OA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G0X8E8_9HIV1 Publication Abstract from PubMed Antiretroviral therapy for HIV-1 infection/AIDS has significantly extended the life expectancy of HIV-1-infected individuals and reduced HIV-1 transmission at very high rates. However, certain individuals who initially achieve viral suppression to undetectable levels may eventually suffer treatment failure mainly due to adverse effects and the emergence of drug-resistant HIV-1 variants. Here, we report GRL-142, a novel HIV-1 protease inhibitor containing an unprecedented 6-5-5-ring-fused crown-like tetrahydropyranofuran, which has extremely potent activity against all HIV-1 strains examined with IC50 values of attomolar-to-picomolar concentrations, virtually no effects on cellular growth, extremely high genetic barrier against the emergence of drug-resistant variants, and favorable intracellular and central nervous system penetration. GRL-142 forms optimum polar, van der Waals, and halogen bond interactions with HIV-1 protease and strongly blocks protease dimerization, demonstrating that combined multiple optimizing elements significantly enhance molecular and atomic interactions with a target protein and generate unprecedentedly potent and practically favorable agents. A novel central nervous system-penetrating protease inhibitor overcomes human immunodeficiency virus 1 resistance with unprecedented aM to pM potency.,Aoki M, Hayashi H, Rao KV, Das D, Higashi-Kuwata N, Bulut H, Aoki-Ogata H, Takamatsu Y, Yedidi RS, Davis DA, Hattori SI, Nishida N, Hasegawa K, Takamune N, Nyalapatla PR, Osswald HL, Jono H, Saito H, Yarchoan R, Misumi S, Ghosh AK, Mitsuya H Elife. 2017 Oct 17;6. pii: e28020. doi: 10.7554/eLife.28020. PMID:29039736 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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