1rt6 | pdb_00001rt6

HIV-1 REVERSE TRANSCRIPTASE COMPLEXED WITH UC38

spinqualitylabelsall models 1rt6, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1rt6 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. Ligands: PO4, UC3 NonStd Res: CSD Gene: POL (HIV-1 M:B_HXB2R) Activity: RNA-directed DNA polymerase, with EC number 2.7.7.49 Resources: FirstGlance, OCA, RCSB, PDBsum 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 The carboxanilides are nonnucleoside inhibitors (NNIs) of HIV-1 reverse transcriptase (RT), of potential clinical importance. The compounds differ in potency and in their retention of potency in the face of drug resistance mutations. Whereas UC-84, the prototype compound, only weakly inhibits many RTs bearing single point resistance mutations, inhibition by UC-781 is little affected. It has been proposed that UC-38 and UC-781 may form quaternary complexes with RT at a site other than the known binding pocket of other NNIs. X-ray crystal structures of four HIV-1 RT-carboxanilide complexes (UC-10, UC-38, UC-84, and UC-781) reported here reveal that all four inhibitors bind in the usual NNI site, forming binary 1:1 complexes with RT in the absence of substrates with the amide/thioamide bond in cis conformations. For all four complexes the anilide rings of the inhibitors overlap aromatic rings of many other NNIs bound to RT. In contrast, the second rings of UC-10, UC-84, and UC-781 do not bind in equivalent positions to those of other "two-ring" NNIs such as alpha-APA or HEPT derivatives. The binding modes most closely resemble that of the structurally dissimilar NNI, Cl-TIBO, with a common hydrogen bond between each carboxanilide NH- group and the main-chain carbonyl oxygen of Lys101. The binding modes differ slightly between the UC-10/UC-781 and UC-38/UC-84 pairs of compounds, apparently related to the shorter isopropylmethanoyl substituents of the anilide rings of UC-38/UC-84, which draws these rings closer to residues Tyr181 and Tyr188. This in turn explains the differences in the effect of mutated residues on the binding of these compounds. Crystal structures of HIV-1 reverse transcriptase in complex with carboxanilide derivatives.,Ren J, Esnouf RM, Hopkins AL, Warren J, Balzarini J, Stuart DI, Stammers DK Biochemistry. 1998 Oct 13;37(41):14394-403. PMID:9772165 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Reverse transcriptase

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