3OB7

Human Thymidylate Synthase R163K with Cys 195 covalently modified by Glutathione

3OB7 の概要

• エントリーDOI: 10.2210/pdb3ob7/pdb
• 関連するPDBエントリー: 3H9K 3HB8
• 分子名称: Thymidylate synthase, GLUTATHIONE, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: methyltransferase, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : P04818
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 179574.19

構造登録者

Gibson, L.M.,Celeste, L.R.,Lovelace, L.L.,Lebioda, L. (登録日: 2010-08-06, 公開日: 2010-12-22, 最終更新日: 2023-09-06)

主引用文献

Gibson, L.M.,Celeste, L.R.,Lovelace, L.L.,Lebioda, L.
Structures of human thymidylate synthase R163K with dUMP, FdUMP and glutathione show asymmetric ligand binding.
Acta Crystallogr.,Sect.D, 67:60-66, 2011

PubMed Abstract: Thymidylate synthase (TS) is a well validated target in cancer chemotherapy. Here, a new crystal form of the R163K variant of human TS (hTS) with five subunits per asymmetric part of the unit cell, all with loop 181-197 in the active conformation, is reported. This form allows binding studies by soaking crystals in artificial mother liquors containing ligands that bind in the active site. Using this approach, crystal structures of hTS complexes with FdUMP and dUMP were obtained, indicating that this form should facilitate high-throughput analysis of hTS complexes with drug candidates. Crystal soaking experiments using oxidized glutathione revealed that hTS binds this ligand. Interestingly, the two types of binding observed are both asymmetric. In one subunit of the physiological dimer covalent modification of the catalytic nucleophile Cys195 takes place, while in another dimer a noncovalent adduct with reduced glutathione is formed in one of the active sites.

PubMed: 21206062
DOI: 10.1107/S0907444910044732

実験手法

X-RAY DIFFRACTION (2.75 Å)