6WOX

Thermus thermophilus RNA polymerase initially transcribing complex with 2'dCTP

6WOX の概要

• エントリーDOI: 10.2210/pdb6wox/pdb
• 分子名称: DNA-directed RNA polymerase subunit alpha, 2'-DEOXYCYTIDINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (12 entities in total)
• 機能のキーワード: initially transcribing complex, transcription, transcription-dna-rna complex, transcription/dna/rna
• 由来する生物種: Thermus thermophilus; 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 441212.87

構造登録者

Shin, Y.,Murakami, K.S. (登録日: 2020-04-26, 公開日: 2020-06-10, 最終更新日: 2024-10-23)

主引用文献

Makinen, J.J.,Shin, Y.,Vieras, E.,Virta, P.,Metsa-Ketela, M.,Murakami, K.S.,Belogurov, G.A.
The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases.
Nat Commun, 12:796-796, 2021

PubMed Abstract: RNA polymerases (RNAPs) synthesize RNA from NTPs, whereas DNA polymerases synthesize DNA from 2'dNTPs. DNA polymerases select against NTPs by using steric gates to exclude the 2'OH, but RNAPs have to employ alternative selection strategies. In single-subunit RNAPs, a conserved Tyr residue discriminates against 2'dNTPs, whereas selectivity mechanisms of multi-subunit RNAPs remain hitherto unknown. Here, we show that a conserved Arg residue uses a two-pronged strategy to select against 2'dNTPs in multi-subunit RNAPs. The conserved Arg interacts with the 2'OH group to promote NTP binding, but selectively inhibits incorporation of 2'dNTPs by interacting with their 3'OH group to favor the catalytically-inert 2'-endo conformation of the deoxyribose moiety. This deformative action is an elegant example of an active selection against a substrate that is a substructure of the correct substrate. Our findings provide important insights into the evolutionary origins of biopolymers and the design of selective inhibitors of viral RNAPs.

PubMed: 33542236
DOI: 10.1038/s41467-021-21005-w

実験手法

X-RAY DIFFRACTION (3.14 Å)