4LRR

Ternary complex between E. coli thymidylate synthase, dUMP, and F9

4LRR の概要

• エントリーDOI: 10.2210/pdb4lrr/pdb
• 関連するPDBエントリー: 4LRP
• 分子名称: Thymidylate synthase, SULFATE ION, 2-oxo-2H-naphtho[1,8-bc]furan-6-yl 4-nitrobenzoate, ... (5 entities in total)
• 機能のキーワード: thymidine monophosphate synthesis, n-terminal acetylated methionine, beta-mercaptoethanol modified cysteine, transferase
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm (By similarity): P0A886
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31999.74

構造登録者

Mangani, S.,Pozzi, C.,Ferrari, S.,Costi, M.P. (登録日: 2013-07-20, 公開日: 2013-11-06, 最終更新日: 2025-03-26)

主引用文献

Ferrari, S.,Calo, S.,Leone, R.,Luciani, R.,Costantino, L.,Sammak, S.,Di Pisa, F.,Pozzi, C.,Mangani, S.,Costi, M.P.
2'-Deoxyuridine 5'-Monophosphate Substrate Displacement in Thymidylate Synthase through 6-Hydroxy-2H-naphtho[1,8-bc]furan-2-one Derivatives.
J.Med.Chem., 56:9356-9360, 2013

PubMed Abstract: Thymidylate synthase (TS) is a target for antifolate-based chemotherapies of microbial and human diseases. Here, ligand-based, synthetic, and X-ray crystallography studies led to the discovery of 6-(3-cyanobenzoyloxy)-2-oxo-2H-naphto[1,8-bc]furan, a novel inhibitor with a Ki of 310 nM against Pneumocystis carinii TS. The X-ray ternary complex with Escherichia coli TS revealed, for the first time, displacement of the substrate toward the dimeric protein interface, thus providing new opportunities for further design of specific inhibitors of microbial pathogens.

PubMed: 24147825
DOI: 10.1021/jm4014086

実験手法

X-RAY DIFFRACTION (2.41 Å)