title: Crystal structure of Thermus thermophilus Delta1-pyrroline-5-carboxylate dehydrogenase.
abstract: Delta(1)-pyrroline-5-carboxylate dehydrogenase (P5CDh) plays an important role in the metabolic pathway from proline to glutamate. It irreversibly catalyzes the oxidation of glutamate-gamma-semialdehyde, the product of the non-enzymatic hydrolysis of Delta(1)-pyrroline-5-carboxylate, into glutamate with the reduction of NAD(+) into NADH. We have confirmed the P5CDh activity of the Thermus thermophilus protein TT0033 (TtP5CDh), and determined the crystal structure of the enzyme in the ligand-free form at 1.4 A resolution. To investigate the structural basis of TtP5CDh function, the TtP5CDh structures with NAD(+), with NADH, and with its product glutamate were determined at 1.8 A, 1.9 A, and 1.4 A resolution, respectively. The solved structures suggest an overall view of the P5CDh catalytic mechanism and provide insights into the P5CDh deficiencies in the case of the human type II hyperprolinemia.
authors.affiliation: RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Inagaki
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Ohshima
authors.forename: Hitomi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Chizu
authors.initials: C
authors.lastname: Kuroishi
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Tahir H
authors.initials: TH
authors.lastname: Tahirov
mesh_terms: D050842:1-Pyrroline-5-Carboxylate Dehydrogenase / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D011392:Proline / Q000097:blood; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D016963:Thermus thermophilus / Q000201:enzymology* / Q000235:genetics
chemical_list: D021122:Protein Subunits; D009243:NAD; D011392:Proline; D050842:1-Pyrroline-5-Carboxylate Dehydrogenase