1DQX

CRYSTAL STRUCTURE OF OROTIDINE 5'-PHOSPHATE DECARBOXYLASE COMPLEXED TO 6-HYDROXYURIDINE 5'-PHOSPHATE (BMP)

1DQX の概要

• エントリーDOI: 10.2210/pdb1dqx/pdb
• 関連するPDBエントリー: 1DQW
• 分子名称: OROTIDINE 5'-PHOSPHATE DECARBOXYLASE, 6-HYDROXYURIDINE-5'-PHOSPHATE (3 entities in total)
• 機能のキーワード: orotidine 5'phosphate decarboxylase, uridine 5'phosphate, ump, omp, 6-hydroxyuridine 5'-phosphate, bmp, tim barrel, lyase
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 118751.07

構造登録者

Milburn, M.V.,Miller, B.G.,Hassell, A.M.,Wolfenden, R.,Short, S.A. (登録日: 2000-01-05, 公開日: 2000-03-20, 最終更新日: 2024-02-07)

主引用文献

Miller, B.G.,Hassell, A.M.,Wolfenden, R.,Milburn, M.V.,Short, S.A.
Anatomy of a proficient enzyme: the structure of orotidine 5'-monophosphate decarboxylase in the presence and absence of a potential transition state analog.
Proc.Natl.Acad.Sci.USA, 97:2011-2016, 2000

PubMed Abstract: Orotidine 5'-phosphate decarboxylase produces the largest rate enhancement that has been reported for any enzyme. The crystal structure of the recombinant Saccharomyces cerevisiae enzyme has been determined in the absence and presence of the proposed transition state analog 6-hydroxyuridine 5'-phosphate, at a resolution of 2.1 A and 2.4 A, respectively. Orotidine 5'-phosphate decarboxylase folds as a TIM-barrel with the ligand binding site near the open end of the barrel. The binding of 6-hydroxyuridine 5'-phosphate is accompanied by protein loop movements that envelop the ligand almost completely, forming numerous favorable interactions with the phosphoryl group, the ribofuranosyl group, and the pyrimidine ring. Lysine-93 appears to be anchored in such a way as to optimize electrostatic interactions with developing negative charge at C-6 of the pyrimidine ring, and to donate the proton that replaces the carboxylate group at C-6 of the product. In addition, H-bonds from the active site to O-2 and O-4 help to delocalize negative charge in the transition state. Interactions between the enzyme and the phosphoribosyl group anchor the pyrimidine within the active site, helping to explain the phosphoribosyl group's remarkably large contribution to catalysis despite its distance from the site of decarboxylation.

PubMed: 10681417
DOI: 10.1073/pnas.030409797

実験手法

X-RAY DIFFRACTION (2.4 Å)