6AUI

Human ribonucleotide reductase large subunit (alpha) with dATP and CDP

6AUI の概要

• エントリーDOI: 10.2210/pdb6aui/pdb
• EMDBエントリー: 7006
• 分子名称: Ribonucleoside-diphosphate reductase large subunit, 2'-DEOXYADENOSINE 5'-TRIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: ribonucleotide reductase electron transfer radical chemistry thiyl radical, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 562707.25

構造登録者

Brignole, E.J.,Drennan, C.L.,Asturias, F.J.,Tsai, K.L.,Penczek, P.A. (登録日: 2017-09-01, 公開日: 2018-04-18, 最終更新日: 2024-03-13)

主引用文献

Brignole, E.J.,Tsai, K.L.,Chittuluru, J.,Li, H.,Aye, Y.,Penczek, P.A.,Stubbe, J.,Drennan, C.L.,Asturias, F.
3.3- angstrom resolution cryo-EM structure of human ribonucleotide reductase with substrate and allosteric regulators bound.
Elife, 7:-, 2018

PubMed Abstract: Ribonucleotide reductases (RNRs) convert ribonucleotides into deoxyribonucleotides, a reaction essential for DNA replication and repair. Human RNR requires two subunits for activity, the α subunit contains the active site, and the β subunit houses the radical cofactor. Here, we present a 3.3-Å resolution structure by cryo-electron microscopy (EM) of a dATP-inhibited state of human RNR. This structure, which was determined in the presence of substrate CDP and allosteric regulators ATP and dATP, has three α units arranged in an α ring. At near-atomic resolution, these data provide insight into the molecular basis for CDP recognition by allosteric specificity effectors dATP/ATP. Additionally, we present lower-resolution EM structures of human α in the presence of both the anticancer drug clofarabine triphosphate and β. Together, these structures support a model for RNR inhibition in which β is excluded from binding in a radical transfer competent position when α exists as a stable hexamer.

PubMed: 29460780
DOI: 10.7554/eLife.31502

実験手法

ELECTRON MICROSCOPY (3.3 Å)