1TSD

THYMIDYLATE SYNTHASE COMPLEX WITH 2'-DEOXYURIDINE 5'-MONOPHOSPHATE (DUMP) AND FOLATE ANALOG 1843U89

1TSD の概要

• エントリーDOI: 10.2210/pdb1tsd/pdb
• 分子名称: THYMIDYLATE SYNTHASE, BETA-MERCAPTOETHANOL, 2'-DEOXYURIDINE 5'-MONOPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: dump, 1843u89, transferase (methyltransferase)
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62860.96

構造登録者

Weichsel, A.,Montfort, W.R. (登録日: 1995-08-15, 公開日: 1996-01-29, 最終更新日: 2025-03-26)

主引用文献

Weichsel, A.,Montfort, W.R.
Ligand-induced distortion of an active site in thymidylate synthase upon binding anticancer drug 1843U89.
Nat.Struct.Biol., 2:1095-1101, 1995

PubMed Abstract: The anticancer drug 1843U89 inhibits thymidylate synthase (TS) at sub-nanomolar concentrations and is undergoing clinical trial. The 1.95 A crystal structure of Escherichia coli TS bound to the drug and dUMP reveals that the 1843U89 binding surface includes a hydrophobic patch that is normally buried. To reach this patch, 1843U89 inserts into the wall of the TS active site, resulting in a severe local distortion of the protein. In this new conformation, active-site groups that normally bind to the catalytic cofactor methylene-tetrahydrofolate instead bind to 1843U89 in new ways. This structure provides a rare example of a protein that can bind tightly to distinct substances using a single, flexible, binding surface. This has implications for drug design, as 1843U89 could not have been obtained from current structure-based approaches.

PubMed: 8846221
DOI: 10.1038/nsb1295-1095

実験手法

X-RAY DIFFRACTION (1.95 Å)