1U1D

Structure of e. coli uridine phosphorylase complexed to 5-(phenylthio)acyclouridine (ptau)

1U1D の概要

• エントリーDOI: 10.2210/pdb1u1d/pdb
• 関連するPDBエントリー: 1TGV 1TGW 1TGY 1U1C 1U1E 1U1F 1U1G
• 分子名称: Uridine phosphorylase, PHOSPHATE ION, POTASSIUM ION, ... (5 entities in total)
• 機能のキーワード: pyrimidine nucleoside phosphorylase; uridine salvage; ptau; 5-(phenylthio)acyclouridine, transferase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 167281.08

構造登録者

Bu, W.,Settembre, E.C.,Ealick, S.E. (登録日: 2004-07-15, 公開日: 2005-07-05, 最終更新日: 2024-02-14)

主引用文献

Bu, W.,Settembre, E.C.,el Kouni, M.H.,Ealick, S.E.
Structural basis for inhibition of Escherichia coli uridine phosphorylase by 5-substituted acyclouridines.
Acta Crystallogr.,Sect.D, 61:863-872, 2005

PubMed Abstract: Uridine phosphorylase (UP) catalyzes the reversible phosphorolysis of uridine to uracil and ribose 1-phosphate and is a key enzyme in the pyrimidine-salvage pathway. Escherichia coli UP is structurally homologous to E. coli purine nucleoside phosphorylase and other members of the type I family of nucleoside phosphorylases. The structures of 5-benzylacyclouridine, 5-phenylthioacyclouridine, 5-phenylselenenylacyclouridine, 5-m-benzyloxybenzyl acyclouridine and 5-m-benzyloxybenzyl barbituric acid acyclonucleoside bound to the active site of E. coli UP have been determined, with resolutions ranging from 1.95 to 2.3 A. For all five complexes the acyclo sugar moiety binds to the active site in a conformation that mimics the ribose ring of the natural substrates. Surprisingly, the terminal hydroxyl group occupies the position of the nonessential 5'-hydroxyl substituent of the substrate rather than the 3'-hydroxyl group, which is normally required for catalytic activity. Until recently, inhibitors of UP were designed with limited structural knowledge of the active-site residues. These structures explain the basis of inhibition for this series of acyclouridine analogs and suggest possible additional avenues for future drug-design efforts. Furthermore, the studies can be extended to design inhibitors of human UP, for which no X-ray structure is available.

PubMed: 15983408
DOI: 10.1107/S0907444905007882

実験手法

X-RAY DIFFRACTION (2.001 Å)