1UAQ

The crystal structure of yeast cytosine deaminase

1UAQ の概要

• エントリーDOI: 10.2210/pdb1uaq/pdb
• 関連するPDBエントリー: 1k70
• 分子名称: cytosine deaminase, ZINC ION, DIHYDROPYRIMIDINE-2,4(1H,3H)-DIONE, ... (4 entities in total)
• 機能のキーワード: alpha-beta-alpha, hydrolase
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35419.06

構造登録者

Ko, T.-P.,Lin, J.-J.,Hu, C.-Y.,Hsu, Y.-H.,Wang, A.H.-J.,Liaw, S.-H. (登録日: 2003-03-14, 公開日: 2003-04-29, 最終更新日: 2023-12-27)

主引用文献

Ko, T.-P.,Lin, J.-J.,Hu, C.-Y.,Hsu, Y.-H.,Wang, A.H.-J.,Liaw, S.-H.
Crystal structure of yeast cytosine deaminase. Insights into enzyme mechanism and evolution
J.Biol.Chem., 278:19111-19117, 2003

PubMed Abstract: Yeast cytosine deaminase is an attractive candidate for anticancer gene therapy because it catalyzes the deamination of the prodrug 5-fluorocytosine to form 5-fluorouracil. We report here the crystal structure of the enzyme in complex with the inhibitor 2-hydroxypyrimidine at 1.6-A resolution. The protein forms a tightly packed dimer with an extensive interface of 1450 A2 per monomer. The inhibitor was converted into a hydrated adduct as a transition-state analog. The essential zinc ion is ligated by the 4-hydroxyl group of the inhibitor together with His62, Cys91, and Cys94 from the protein. The enzyme shares similar active-site architecture to cytidine deaminases and an unusually high structural homology to 5-aminoimidazole-4-carboxamide-ribonucleotide transformylase and thereby may define a new superfamily. The unique C-terminal tail is involved in substrate specificity and also functions as a gate controlling access to the active site. The complex structure reveals a closed conformation, suggesting that substrate binding seals the active-site entrance so that the catalytic groups are sequestered from solvent. A comparison of the crystal structures of the bacterial and fungal cytosine deaminases provides an elegant example of convergent evolution, where starting from unrelated ancestral proteins, the same metal-assisted deamination is achieved through opposite chiral intermediates within distinctly different active sites.

PubMed: 12637534
DOI: 10.1074/jbc.M300874200

実験手法

X-RAY DIFFRACTION (1.6 Å)