4EB4

Crystal structure of mouse thymidylate synthase in ternary complex with dUMP and Tomudex

4EB4 の概要

• エントリーDOI: 10.2210/pdb4eb4/pdb
• 分子名称: Thymidylate synthase, 2'-DEOXYURIDINE 5'-MONOPHOSPHATE, TOMUDEX, ... (8 entities in total)
• 機能のキーワード: ternary complex, methyltransferase, nucleotide biosynthesis, transferase
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Nucleus : P07607
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 144437.23

構造登録者

Dowiercial, A.,Jarmula, A.,Rypniewski, W.R.,Wilk, P.,Rode, W. (登録日: 2012-03-23, 公開日: 2012-05-02, 最終更新日: 2024-02-28)

主引用文献

Dowiercial, A.,Wilk, P.,Rypniewski, W.,Rode, W.,Jarmula, A.
Crystal structure of mouse thymidylate synthase in tertiary complex with dUMP and raltitrexed reveals N-terminus architecture and two different active site conformations.
Biomed Res Int, 2014:945803-, 2014

PubMed Abstract: The crystal structure of mouse thymidylate synthase (mTS) in complex with substrate dUMP and antifolate inhibitor Raltitrexed is reported. The structure reveals, for the first time in the group of mammalian TS structures, a well-ordered segment of 13 N-terminal amino acids, whose ordered conformation is stabilized due to specific crystal packing. The structure consists of two homodimers, differing in conformation, one being more closed (dimer AB) and thus supporting tighter binding of ligands, and the other being more open (dimer CD) and thus allowing weaker binding of ligands. This difference indicates an asymmetrical effect of the binding of Raltitrexed to two independent mTS molecules. Conformational changes leading to a ligand-induced closing of the active site cleft are observed by comparing the crystal structures of mTS in three different states along the catalytic pathway: ligand-free, dUMP-bound, and dUMP- and Raltitrexed-bound. Possible interaction routes between hydrophobic residues of the mTS protein N-terminal segment and the active site are also discussed.

PubMed: 24995339
DOI: 10.1155/2014/945803

実験手法

X-RAY DIFFRACTION (1.74 Å)