2G5C
Crystal Structure of Prephenate Dehydrogenase from Aquifex aeolicus
Summary for 2G5C
| Entry DOI | 10.2210/pdb2g5c/pdb |
| Descriptor | prephenate dehydrogenase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total) |
| Functional Keywords | prephenate dehydrogenase, tyra, oxidoreductase |
| Biological source | Aquifex aeolicus |
| Total number of polymer chains | 4 |
| Total formula weight | 130572.55 |
| Authors | Sun, W.,Singh, S.,Zhang, R.,Turnbull, J.L.,Christendat, D. (deposition date: 2006-02-22, release date: 2006-03-07, Last modification date: 2011-07-13) |
| Primary citation | 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 Cited by 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: 16513644DOI: 10.1074/jbc.M511986200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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