2OPR

Crystal Structure of K101E Mutant HIV-1 Reverse Transcriptase in Complex with GW420867X.

2OPR の概要

• エントリーDOI: 10.2210/pdb2opr/pdb
• 分子名称: Reverse transcriptase/ribonuclease H, p51 RT, ISOPROPYL (2S)-2-ETHYL-7-FLUORO-3-OXO-3,4-DIHYDROQUINOXALINE-1(2H)-CARBOXYLATE (3 entities in total)
• 機能のキーワード: hiv-1 reverse transcriptase, aids, nnrti, gw420867x, drug resistance, transferase
• 由来する生物種: HIV-1 M:B_HXB2R; 詳細
• 細胞内の位置: Matrix protein p17: Virion . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P04585 P04585
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 113441.80

構造登録者

Ren, J.,Nichols, C.E.,Chamberlain, P.P.,Weaver, K.L.,Short, S.A.,Chan, J.H.,Kleim, J.,Stammers, D.K. (登録日: 2007-01-30, 公開日: 2007-05-22, 最終更新日: 2024-11-20)

主引用文献

Ren, J.,Nichols, C.E.,Chamberlain, P.P.,Weaver, K.L.,Short, S.A.,Chan, J.H.,Kleim, J.P.,Stammers, D.K.
Relationship of Potency and Resilience to Drug Resistant Mutations for GW420867X Revealed by Crystal Structures of Inhibitor Complexes for Wild-Type, Leu100Ile, Lys101Glu, and Tyr188Cys Mutant HIV-1 Reverse Transcriptases.
J.Med.Chem., 50:2301-2309, 2007

PubMed Abstract: The selection of drug resistant viruses is a major problem in efforts to combat HIV and AIDS, hence, new compounds are required. We report crystal structures of wild-type and mutant HIV-1 RT with bound non-nucleoside (NNRTI) GW420867X, aimed at investigating the basis for its high potency and improved drug resistance profile compared to the first-generation drug nevirapine. GW420867X occupies a smaller volume than many NNRTIs, yet accesses key regions of the binding pocket. GW420867X has few contacts with Tyr188, hence, explaining the small effect of mutating this residue on inhibitor-binding potency. In a mutated NNRTI pocket, GW420867X either remains in a similar position compared to wild-type (RT(Leu100Ile) and RT(Tyr188Cys)) or rearranges within the pocket (RT(Lys101Glu)). For RT(Leu100Ile), GW420867X does not shift position, in spite of forming different side-chain contacts. The small bulk of GW420867X allows adaptation to a mutated NNRTI binding site by repositioning or readjustment of side-chain contacts with only small reductions in binding affinity.

PubMed: 17441703
DOI: 10.1021/jm061117m

実験手法

X-RAY DIFFRACTION (2.9 Å)