3GGP
Crystal structure of prephenate dehydrogenase from A. aeolicus in complex with hydroxyphenyl propionate and NAD+
Summary for 3GGP
| Entry DOI | 10.2210/pdb3ggp/pdb |
| Related | 3GGG 3ggo |
| Descriptor | Prephenate dehydrogenase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, CHLORIDE ION, ... (5 entities in total) |
| Functional Keywords | hydroxyphenyl propionate, tyra, prephenate dehydrogenase, alpha-beta, oxidoreductase |
| Biological source | Aquifex aeolicus |
| Total number of polymer chains | 4 |
| Total formula weight | 144112.05 |
| Authors | Sun, W.,Shahinas, D.,Kimber, M.S.,Christendat, D. (deposition date: 2009-03-01, release date: 2009-03-10, Last modification date: 2023-09-06) |
| Primary citation | Sun, W.,Shahinas, D.,Bonvin, J.,Hou, W.,Kimber, M.S.,Turnbull, J.,Christendat, D. The Crystal Structure of Aquifex aeolicus Prephenate Dehydrogenase Reveals the Mode of Tyrosine Inhibition. J.Biol.Chem., 284:13223-13232, 2009 Cited by PubMed Abstract: TyrA proteins belong to a family of dehydrogenases that are dedicated to l-tyrosine biosynthesis. The three TyrA subclasses are distinguished by their substrate specificities, namely the prephenate dehydrogenases, the arogenate dehydrogenases, and the cyclohexadienyl dehydrogenases, which utilize prephenate, l-arogenate, or both substrates, respectively. The molecular mechanism responsible for TyrA substrate selectivity and regulation is unknown. To further our understanding of TyrA-catalyzed reactions, we have determined the crystal structures of Aquifex aeolicus prephenate dehydrogenase bound with NAD(+) plus either 4-hydroxyphenylpyuvate, 4-hydroxyphenylpropionate, or l-tyrosine and have used these structures as guides to target active site residues for site-directed mutagenesis. From a combination of mutational and structural analyses, we have demonstrated that His-147 and Arg-250 are key catalytic and binding groups, respectively, and Ser-126 participates in both catalysis and substrate binding through the ligand 4-hydroxyl group. The crystal structure revealed that tyrosine, a known inhibitor, binds directly to the active site of the enzyme and not to an allosteric site. The most interesting finding though, is that mutating His-217 relieved the inhibitory effect of tyrosine on A. aeolicus prephenate dehydrogenase. The identification of a tyrosine-insensitive mutant provides a novel avenue for designing an unregulated enzyme for application in metabolic engineering. PubMed: 19279014DOI: 10.1074/jbc.M806272200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
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