2QKK

Human RNase H catalytic domain mutant D210N in complex with 14-mer RNA/DNA hybrid

2QKK の概要

• エントリーDOI: 10.2210/pdb2qkk/pdb
• 関連するPDBエントリー: 2QK9 2QKB
• 分子名称: 5'-R(*CP*GP*AP*CP*AP*CP*CP*UP*GP*AP*UP*UP*CP*C)-3', 5'-D(*GP*GP*AP*AP*TP*CP*AP*GP*GP*TP*GP*TP*CP*G)-3', Ribonuclease H1, ... (8 entities in total)
• 機能のキーワード: rnase h; rna/dna hybrid, hydrolase-dna-rna complex, hydrolase/dna/rna
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (Potential): O60930
• タンパク質・核酸の鎖数: 23
• 化学式量合計: 241521.99

構造登録者

Nowotny, M.,Gaidamakov, S.A.,Ghirlando, R.,Cerritelli, S.M.,Crouch, R.J.,Yang, W. (登録日: 2007-07-11, 公開日: 2007-11-13, 最終更新日: 2023-08-30)

主引用文献

Nowotny, M.,Gaidamakov, S.A.,Ghirlando, R.,Cerritelli, S.M.,Crouch, R.J.,Yang, W.
Structure of Human RNase H1 Complexed with an RNA/DNA Hybrid: Insight into HIV Reverse Transcription
Mol.Cell, 28:264-276, 2007

PubMed Abstract: We report here crystal structures of human RNase H1 complexed with an RNA/DNA substrate. Unlike B. halodurans RNase H1, human RNase H1 has a basic protrusion, which forms a DNA-binding channel and together with the conserved phosphate-binding pocket confers specificity for the B form and 2'-deoxy DNA. The RNA strand is recognized by four consecutive 2'-OH groups and cleaved by a two-metal ion mechanism. Although RNase H1 is overall positively charged, the substrate interface is neutral to acidic in character, which likely contributes to the catalytic specificity. Positions of the scissile phosphate and two catalytic metal ions are interdependent and highly coupled. Modeling of HIV reverse transcriptase (RT) with RNA/DNA in its RNase H active site suggests that the substrate cannot simultaneously occupy the polymerase active site and must undergo a conformational change to toggle between the two catalytic centers. The region that accommodates this conformational change offers a target to develop HIV-specific inhibitors.

PubMed: 17964265
DOI: 10.1016/j.molcel.2007.08.015

実験手法

X-RAY DIFFRACTION (3.2 Å)