3JYT

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

3JYT の概要

• エントリーDOI: 10.2210/pdb3jyt/pdb
• 関連するPDBエントリー: 1RTD 1T05 3JSM
• 分子名称: Reverse transcriptase/ribonuclease H, p51 RT, DNA (5'-D(*A*TP*GP*GP*TP*CP*GP*GP*CP*GP*CP*CP*CP*GP*AP*AP*CP*AP*GP*GP*GP*AP*CP*TP*GP*TP*G)-3'), ... (7 entities in total)
• 機能のキーワード: hiv-1 reverse transcriptase, tenofovir, rt-dna complex, transferase-dna complex, drug resistance mutation, aids, dna recombination, dna-directed dna polymerase, rnase h, hydrolase, lipoprotein, magnesium, membrane, metal-binding, multifunctional enzyme, nucleotidyltransferase, rna-directed dna polymerase transferase, transferase-dna complex complex, transferase/dna complex
• 由来する生物種: Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1); 詳細
• 細胞内の位置: Matrix protein p17: Virion (Potential). Capsid protein p24: Virion (Potential). Nucleocapsid protein p7: Virion (Potential). Reverse transcriptase/ribonuclease H: Virion (Potential). Integrase: Virion (Potential): P03366 P03366
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 130962.86

構造登録者

Das, K.,Arnold, E. (登録日: 2009-09-22, 公開日: 2009-10-06, 最終更新日: 2023-09-06)

主引用文献

Das, K.,Bandwar, R.P.,White, K.L.,Feng, J.Y.,Sarafianos, S.G.,Tuske, S.,Tu, X.,Clark, A.D.,Boyer, P.L.,Hou, X.,Gaffney, B.L.,Jones, R.A.,Miller, M.D.,Hughes, S.H.,Arnold, E.
Structural basis for the role of the K65r mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance.
J.Biol.Chem., 284:35092-35100, 2009

PubMed Abstract: 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.

PubMed: 19812032
DOI: 10.1074/jbc.M109.022525

実験手法

X-RAY DIFFRACTION (3.3 Å)