2G5C

Crystal Structure of Prephenate Dehydrogenase from Aquifex aeolicus

2G5C の概要

• エントリーDOI: 10.2210/pdb2g5c/pdb
• 分子名称: prephenate dehydrogenase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: prephenate dehydrogenase, tyra, oxidoreductase
• 由来する生物種: Aquifex aeolicus
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 130572.55

構造登録者

Sun, W.,Singh, S.,Zhang, R.,Turnbull, J.L.,Christendat, D. (登録日: 2006-02-22, 公開日: 2006-03-07, 最終更新日: 2024-11-13)

主引用文献

Sun, W.,Singh, S.,Zhang, R.,Turnbull, J.L.,Christendat, D.
Crystal Structure of Prephenate Dehydrogenase from Aquifex aeolicus: Insights into the Catalytic Mechanism
J.Biol.Chem., 281:12919-12928, 2006

PubMed Abstract: The enzyme prephenate dehydrogenase catalyzes the oxidative decarboxylation of prephenate to 4-hydroxyphenylpyruvate for the biosynthesis of tyrosine. Prephenate dehydrogenases exist as either monofunctional or bifunctional enzymes. The bifunctional enzymes are diverse, since the prephenate dehydrogenase domain is associated with other enzymes, such as chorismate mutase and 3-phosphoskimate 1-carboxyvinyltransferase. We report the first crystal structure of a monofunctional prephenate dehydrogenase enzyme from the hyper-thermophile Aquifex aeolicus in complex with NAD+. This protein consists of two structural domains, a modified nucleotide-binding domain and a novel helical prephenate binding domain. The active site of prephenate dehydrogenase is formed at the domain interface and is shared between the subunits of the dimer. We infer from the structure that access to the active site is regulated via a gated mechanism, which is modulated by an ionic network involving a conserved arginine, Arg250. In addition, the crystal structure reveals for the first time the positions of a number of key catalytic residues and the identity of other active site residues that may participate in the reaction mechanism; these residues include Ser126 and Lys246 and the catalytic histidine, His147. Analysis of the structure further reveals that two secondary structure elements, beta3 and beta7, are missing in the prephenate dehydrogenase domain of the bifunctional chorismate mutase-prephenate dehydrogenase enzymes. This observation suggests that the two functional domains of chorismate mutase-prephenate dehydrogenase are interdependent and explains why these domains cannot be separated.

PubMed: 16513644
DOI: 10.1074/jbc.M511986200

実験手法

X-RAY DIFFRACTION (1.9 Å)