5IOR

Flavin-dependent thymidylate synthase in complex with FAD and 2'-deoxyuridine-5'-monosulfate

5IOR の概要

• エントリーDOI: 10.2210/pdb5ior/pdb
• 関連するPDBエントリー: 5IOQ 5IOS 5IOT
• 分子名称: Thymidylate synthase ThyX, FLAVIN-ADENINE DINUCLEOTIDE, 2'-deoxy-5'-O-sulfouridine, ... (5 entities in total)
• 機能のキーワード: fad-dependent, nucleotide biosynthesis, reductive methylation, transferase
• 由来する生物種: Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28973.86

構造登録者

Bernard, S.M.,Stull, F.W.,Smith, J.L. (登録日: 2016-03-08, 公開日: 2016-06-08, 最終更新日: 2023-09-27)

主引用文献

Stull, F.W.,Bernard, S.M.,Sapra, A.,Smith, J.L.,Zuiderweg, E.R.,Palfey, B.A.
Deprotonations in the Reaction of Flavin-Dependent Thymidylate Synthase.
Biochemistry, 55:3261-3269, 2016

PubMed Abstract: Many microorganisms use flavin-dependent thymidylate synthase (FDTS) to synthesize the essential nucleotide 2'-deoxythymidine 5'-monophosphate (dTMP) from 2'-deoxyuridine 5'-monophosphate (dUMP), 5,10-methylenetetrahydrofolate (CH2THF), and NADPH. FDTSs have a structure that is unrelated to the thymidylate synthase used by humans and a very different mechanism. Here we report nuclear magnetic resonance evidence that FDTS ionizes N3 of dUMP using an active-site arginine. The ionized form of dUMP is largely responsible for the changes in the flavin absorbance spectrum of FDTS upon dUMP binding. dUMP analogues also suggest that the phosphate of dUMP acts as the base that removes the proton from C5 of the dUMP-methylene intermediate in the FDTS-catalyzed reaction. These findings establish additional differences between the mechanisms of FDTS and human thymidylate synthase.

PubMed: 27214228
DOI: 10.1021/acs.biochem.6b00510

実験手法

X-RAY DIFFRACTION (1.95 Å)