1SYN

E. COLI THYMIDYLATE SYNTHASE IN COMPLEX WITH BW1843U89 AND 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP)

1SYN の概要

• エントリーDOI: 10.2210/pdb1syn/pdb
• 分子名称: THYMIDYLATE SYNTHASE, 2'-DEOXYURIDINE 5'-MONOPHOSPHATE, S)-2-(5(((1,2-DIHYDRO-3-METHYL-1-OXOBENZO(F)QUINAZOLIN-9-YL)METHYL)AMINO)1-OXO-2-ISOINDOLINYL)GLUTARIC ACID, ... (4 entities in total)
• 機能のキーワード: transferase (methyltransferase)
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm: P0A884
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62704.69

構造登録者

Stout, T.J.,Stroud, R.M. (登録日: 1995-09-19, 公開日: 1996-01-29, 最終更新日: 2024-06-05)

主引用文献

Stout, T.J.,Stroud, R.M.
The complex of the anti-cancer therapeutic, BW1843U89, with thymidylate synthase at 2.0 A resolution: implications for a new mode of inhibition.
Structure, 4:67-77, 1996

PubMed Abstract: Thymidylate synthase (TS) is critical to DNA synthesis as it catalyzes the rate limiting step in the only biosynthetic pathway for deoxythymidine monophosphate (dTMP) production. TS is therefore an important target for anti-proliferative and anti-cancer drug design. The TS enzymatic mechanism involves the reductive methylation of the substrate, deoxyuridine monophosphate (dUMP), by transfer of a methylene group from the co-factor, methylenetetrahydrofolate (CH2H4folate), resulting in the production of deoxythymidine monophosphate (dTMP) and dihydrofolate (H2folate). Previous drug design efforts based on co-factor analogues have produced good inhibitors of TS, but poor bioavailability and toxicity have limited their usefulness. BW1843U89, a folate analogue, is a recently developed compound which is an exceptionally strong inhibitor (Ki = 0.09 nM), has good bioavailability and in clinical trials thus far has not demonstrated significant toxicity.

PubMed: 8805515
DOI: 10.1016/S0969-2126(96)00010-X

実験手法

X-RAY DIFFRACTION (2 Å)