4ERP

Crystal structure of a gemcitabine-diphosphate inhibited E. coli class Ia ribonucleotide reductase complex

4ERP の概要

• エントリーDOI: 10.2210/pdb4erp/pdb
• 関連するPDBエントリー: 4ERM
• 分子名称: Ribonucleoside-diphosphate reductase 1 subunit alpha, Ribonucleoside-diphosphate reductase 1 subunit beta, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: protein-protein complex, alpha/beta barrel, atp cone, diiron center, oxidoreductase, rnr alpha, rnr beta, thioredoxin, ribonucleotide reduction, cytosol
• 由来する生物種: Escherichia coli K-12; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 519755.28

構造登録者

Zimanyi, C.M.,Drennan, C.L. (登録日: 2012-04-20, 公開日: 2012-07-04, 最終更新日: 2023-09-13)

主引用文献

Zimanyi, C.M.,Ando, N.,Brignole, E.J.,Asturias, F.J.,Stubbe, J.,Drennan, C.L.
Tangled up in knots: structures of inactivated forms of E. coli class Ia ribonucleotide reductase.
Structure, 20:1374-1383, 2012

PubMed Abstract: Ribonucleotide reductases (RNRs) provide the precursors for DNA biosynthesis and repair and are successful targets for anticancer drugs such as clofarabine and gemcitabine. Recently, we reported that dATP inhibits E. coli class Ia RNR by driving formation of RNR subunits into α4β4 rings. Here, we present the first X-ray structure of a gemcitabine-inhibited E. coli RNR and show that the previously described α4β4 rings can interlock to form an unprecedented (α4β4)2 megacomplex. This complex is also seen in a higher-resolution dATP-inhibited RNR structure presented here, which employs a distinct crystal lattice from that observed in the gemcitabine-inhibited case. With few reported examples of protein catenanes, we use data from small-angle X-ray scattering and electron microscopy to both understand the solution conditions that contribute to concatenation in RNRs as well as present a mechanism for the formation of these unusual structures.

PubMed: 22727814
DOI: 10.1016/j.str.2012.05.009

実験手法

X-RAY DIFFRACTION (4.45 Å)