3QIO

Crystal Structure of HIV-1 RNase H with engineered E. coli loop and N-hydroxy quinazolinedione inhibitor

3QIO の概要

• エントリーDOI: 10.2210/pdb3qio/pdb
• 関連するPDBエントリー: 3HYF
• 分子名称: Gag-Pol polyprotein,Ribonuclease HI,Gag-Pol polyprotein, MANGANESE (II) ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: rnase h, hiv-1, inhibitor, nuclease, transferase, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Human immunodeficiency virus type 1 group M subtype B (HIV-1); 詳細
• 細胞内の位置: Gag-Pol polyprotein: Host cell membrane; Lipid-anchor . Matrix protein p17: Virion membrane; Lipid- anchor . Capsid protein p24: Virion . Nucleocapsid protein p7: Virion . Reverse transcriptase/ribonuclease H: Virion . Integrase: Virion : P04585
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17445.71

構造登録者

Lansdon, E.B.,Liu, Q. (登録日: 2011-01-27, 公開日: 2011-04-20, 最終更新日: 2023-09-13)

主引用文献

Lansdon, E.B.,Liu, Q.,Leavitt, S.A.,Balakrishnan, M.,Perry, J.K.,Lancaster-Moyer, C.,Kutty, N.,Liu, X.,Squires, N.H.,Watkins, W.J.,Kirschberg, T.A.
Structural and Binding Analysis of Pyrimidinol Carboxylic Acid and N-Hydroxy Quinazolinedione HIV-1 RNase H Inhibitors.
Antimicrob.Agents Chemother., 55:2905-2915, 2011

PubMed Abstract: HIV-1 RNase H breaks down the intermediate RNA-DNA hybrids during reverse transcription, requiring two divalent metal ions for activity. Pyrimidinol carboxylic acid and N-hydroxy quinazolinedione inhibitors were designed to coordinate the two metal ions in the active site of RNase H. High-resolution (1.4 Å to 2.1 Å) crystal structures were determined with the isolated RNase H domain and reverse transcriptase (RT), which permit accurate assessment of the metal and water environment at the active site. The geometry of the metal coordination suggests that the inhibitors mimic a substrate state prior to phosphodiester catalysis. Surface plasmon resonance studies confirm metal-dependent binding to RNase H and demonstrate that the inhibitors do not bind at the polymerase active site of RT. Additional evaluation of the RNase H site reveals an open protein surface with few additional interactions to optimize active-site inhibitors.

PubMed: 21464257
DOI: 10.1128/AAC.01594-10

実験手法

X-RAY DIFFRACTION (1.4011 Å)