3O7I

Crystal structure of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase from Klebsiella pneumoniae

3O7I の概要

• エントリーDOI: 10.2210/pdb3o7i/pdb
• 関連するPDBエントリー: 3O7H 3O7J 3O7K
• 分子名称: OHCU decarboxylase (2 entities in total)
• 機能のキーワード: decarboxylase, lyase
• 由来する生物種: Klebsiella pneumoniae subsp. pneumoniae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41666.59

構造登録者

French, J.B.,Ealick, S.E. (登録日: 2010-07-30, 公開日: 2010-09-08, 最終更新日: 2024-02-21)

主引用文献

French, J.B.,Ealick, S.E.
Structural and Mechanistic Studies on Klebsiella pneumoniae 2-Oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline Decarboxylase.
J.Biol.Chem., 285:35446-35454, 2010

PubMed Abstract: The stereospecific oxidative degradation of uric acid to (S)-allantoin was recently shown to proceed via three enzymatic steps. The final conversion is a decarboxylation of the unstable intermediate 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) and is catalyzed by OHCU decarboxylase. Here we present the structures of Klebsiella pneumoniae OHCU decarboxylase in unliganded form and with bound allantoin. These structures provide evidence that ligand binding organizes the active site residues for catalysis. Modeling of the substrate and intermediates provides additional support for this hypothesis. In addition we characterize the steady state kinetics of this enzyme and report the first OHCU decarboxylase inhibitor, allopurinol, a structural isomer of hypoxanthine. This molecule is a competitive inhibitor of K. pneumoniae OHCU decarboxylase with a K(i) of 30 ± 2 μM. Circular dichroism measurements confirm structural observations that this inhibitor disrupts the necessary organization of the active site. Our structural and biochemical studies also provide further insights into the mechanism of catalysis of OHCU decarboxylation.

PubMed: 20826786
DOI: 10.1074/jbc.M110.156034

実験手法

X-RAY DIFFRACTION (1.5 Å)