6CTK

Ternary complex crystal structure of DNA polymerase Beta with a dideoxy terminated primer with CHF-R/S isomers, beta, gamma dTTP analogue

6CTK の概要

• エントリーDOI: 10.2210/pdb6ctk/pdb
• 分子名称: DNA (5'-D(*CP*CP*GP*AP*CP*AP*GP*CP*GP*CP*AP*TP*CP*AP*GP*C)-3'), DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*(DOC))-3'), DNA (5'-D(P*GP*TP*CP*GP*G)-3'), ... (8 entities in total)
• 機能のキーワード: dna polymerase beta, conformational change, enzyme mechanism, lfer, transcription-dna complex, transcription/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 48309.41

構造登録者

Batra, V.K.,Wilson, S.H. (登録日: 2018-03-23, 公開日: 2018-06-20, 最終更新日: 2023-10-04)

主引用文献

Batra, V.K.,Oertell, K.,Beard, W.A.,Kashemirov, B.A.,McKenna, C.E.,Goodman, M.F.,Wilson, S.H.
Mapping Functional Substrate-Enzyme Interactions in the pol beta Active Site through Chemical Biology: Structural Responses to Acidity Modification of Incoming dNTPs.
Biochemistry, 57:3934-3944, 2018

PubMed Abstract: We report high-resolution crystal structures of DNA polymerase (pol) β in ternary complex with a panel of incoming dNTPs carrying acidity-modified 5'-triphosphate groups. These novel dNTP analogues have a variety of halomethylene substitutions replacing the bridging oxygen between Pβ and Pγ of the incoming dNTP, whereas other analogues have alkaline substitutions at the bridging oxygen. Use of these analogues allows the first systematic comparison of effects of 5'-triphosphate acidity modification on active site structures and the rate constant of DNA synthesis. These ternary complex structures with incoming dATP, dTTP, and dCTP analogues reveal the enzyme's active site is not grossly altered by the acidity modifications of the triphosphate group, yet with analogues of all three incoming dNTP bases, subtle structural differences are apparent in interactions around the nascent base pair and at the guanidinium groups of active site arginine residues. These results are important for understanding how acidity modification of the incoming dNTP's 5'-triphosphate can influence DNA polymerase activity and the significance of interactions at arginines 183 and 149 in the active site.

PubMed: 29874056
DOI: 10.1021/acs.biochem.8b00418

実験手法

X-RAY DIFFRACTION (2.153 Å)