3WK2

Orotidine 5'-monophosphate decarboxylase K72A mutant from M. thermoautotrophicus complexed with orotidine 5'-monophosphate methyl ester

3WK2 の概要

• エントリーDOI: 10.2210/pdb3wk2/pdb
• 関連するPDBエントリー: 3WJW 3WJX 3WJY 3WK0 3WK1 3WK3 3WKZ
• 分子名称: Orotidine 5'-phosphate decarboxylase, 6-(methoxycarbonyl)uridine 5'-(dihydrogen phosphate), GLYCEROL, ... (4 entities in total)
• 機能のキーワード: protein-ligand complex, tim barrel, decarboxylase, pyrimidine biosynthesis, lyase
• 由来する生物種: Methanothermobacter thermautotrophicus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 27887.70

構造登録者

Fujihashi, M.,Pai, E.F.,Miki, K. (登録日: 2013-10-17, 公開日: 2013-12-04, 最終更新日: 2023-11-08)

主引用文献

Fujihashi, M.,Ishida, T.,Kuroda, S.,Kotra, L.P.,Pai, E.F.,Miki, K.
Substrate distortion contributes to the catalysis of orotidine 5'-monophosphate decarboxylase.
J.Am.Chem.Soc., 135:17432-17443, 2013

PubMed Abstract: Orotidine 5'-monophosphate decarboxylase (ODCase) accelerates the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP) by 17 orders of magnitude. Eight new crystal structures with ligand analogues combined with computational analyses of the enzyme's short-lived intermediates and the intrinsic electronic energies to distort the substrate and other ligands improve our understanding of the still controversially discussed reaction mechanism. In their respective complexes, 6-methyl-UMP displays significant distortion of its methyl substituent bond, 6-amino-UMP shows the competition between the K72 and C6 substituents for a position close to D70, and the methyl and ethyl esters of OMP both induce rotation of the carboxylate group substituent out of the plane of the pyrimidine ring. Molecular dynamics and quantum mechanics/molecular mechanics computations of the enzyme-substrate complex also show the bond between the carboxylate group and the pyrimidine ring to be distorted, with the distortion contributing a 10-15% decrease of the ΔΔG(⧧) value. These results are consistent with ODCase using both substrate distortion and transition-state stabilization, primarily exerted by K72, in its catalysis of the OMP decarboxylation reaction.

PubMed: 24151964
DOI: 10.1021/ja408197k

実験手法

X-RAY DIFFRACTION (1.69 Å)