3jsm

K65R mutant HIV-1 reverse transcriptase cross-linked to DS-DNA and complexed with tenofovir-diphosphate as the incoming nucleotide substrateK65R mutant HIV-1 reverse transcriptase cross-linked to DS-DNA and complexed with tenofovir-diphosphate as the incoming nucleotide substrate

Structural highlights 3jsm is a 4 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. Ligands: , , NonStd Res: , Related: 1t05, 1rtd, 3jyt Gene: gag-pol, POL (Human immunodeficiency virus 1) 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 K65R is a primary reverse transcriptase (RT) mutation selected in human immunodeficiency virus type 1-infected patients taking antiretroviral regimens containing tenofovir disoproxil fumarate or other nucleoside analog RT drugs. We determined the crystal structures of K65R mutant RT cross-linked to double-stranded DNA and in complexes with tenofovir diphosphate (TFV-DP) or dATP. The crystals permit substitution of TFV-DP with dATP at the dNTP-binding site. The guanidinium planes of the arginines K65R and Arg(72) were stacked to form a molecular platform that restricts the conformational adaptability of both of the residues, which explains the negative effects of the K65R mutation on nucleotide incorporation and on excision. Furthermore, the guanidinium planes of K65R and Arg(72) were stacked in two different rotameric conformations in TFV-DP- and dATP-bound structures that may help explain how K65R RT discriminates the drug from substrates. These K65R-mediated effects on RT structure and function help us to visualize the complex interaction with other key nucleotide RT drug resistance mutations, such as M184V, L74V, and thymidine analog resistance mutations. Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance.,Das K, Bandwar RP, White KL, Feng JY, Sarafianos SG, Tuske S, Tu X, Clark AD Jr, Boyer PL, Hou X, Gaffney BL, Jones RA, Miller MD, Hughes SH, Arnold E J Biol Chem. 2009 Dec 11;284(50):35092-100. Epub 2009 Oct 7. PMID:19812032 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Reverse transcriptase

spinqualitylabelsall models 3jsm, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image