3dmj | pdb_00003dmj

CRYSTAL STRUCTURE OF HIV-1 V106A and Y181C MUTANT REVERSE TRANSCRIPTASE IN COMPLEX WITH GW564511.

spinqualitylabelsall models 3dmj, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3dmj is a 2 chain structure with sequence from HIV-1 M:B_HXB2R. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: CSD, GWE, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A7YKL0_9HIV1 Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Owing to the emergence of resistant virus, next generation non-nucleoside HIV reverse transcriptase inhibitors (NNRTIs) with improved drug resistance profiles have been developed to treat HIV infection. Crystal structures of HIV-1 RT complexed with benzophenones optimized for inhibition of HIV mutants that were resistant to the prototype benzophenone GF128590 indicate factors contributing to the resilience of later compounds in the series (GW4511, GW678248). Meta-substituents on the benzophenone A-ring had the designed effect of inducing better contacts with the conserved W229 while reducing aromatic stacking interactions with the highly mutable Y181 side chain, which unexpectedly adopted a "down" position. Up to four main-chain hydrogen bonds to the inhibitor also appear significant in contributing to resilience. Structures of mutant RTs (K103N, V106A/Y181C) with benzophenones showed only small rearrangements of the NNRTIs relative to wild-type. Hence, adaptation to a mutated NNRTI pocket by inhibitor rearrangement appears less significant for benzophenones than other next-generation NNRTIs. Structural basis for the improved drug resistance profile of new generation benzophenone non-nucleoside HIV-1 reverse transcriptase inhibitors.,Ren J, Chamberlain PP, Stamp A, Short SA, Weaver KL, Romines KR, Hazen R, Freeman A, Ferris RG, Andrews CW, Boone L, Chan JH, Stammers DK J Med Chem. 2008 Aug 28;51(16):5000-8. Epub 2008 Jul 30. PMID:18665583 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Reverse transcriptase 3D structures

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