title: Crystal structure of serine dehydrogenase from Escherichia coli: important role of the C-terminal region for closed-complex formation.
abstract: Serine dehydrogenase from Escherichia coli is a homotetrameric enzyme belonging to the short-chain dehydrogenase/reductase (SDR) family. This enzyme catalyses the NADP(+)-dependent oxidation of serine to 2-aminomalonate semialdehyde. The enzyme shows a stereospecificity for β-(3S)-hydroxy acid as a substrate; however, no stereospecificity was observed at the α-carbon. The structures of the ligand-free SerDH and SerDH-NADP(+)-phosphate complex were determined at 1.9 and 2.7 Å resolutions, respectively. The overall structure, including the catalytic tetrad of Asn106, Ser134, Tyr147 and Lys151, shows obvious relationships with other members of the SDR family. The structure of the substrate-binding loop and that of the C-terminal region were disordered in the ligand-free enzyme, whereas these structures were clearly defined in the SerDH-NADP(+) complex as a closed form. Interestingly, the C-terminal region was protruded from the main body and it formed an anti-parallel β-sheet with another C-terminal region on the subunit that is diagonally opposite to that in the tetramer. It is revealed that the C-terminal region possesses the important roles in substrate binding through the stabilization of the substrate-binding loop in the closed form complex. The roles of the C-terminal region along with those of the residues involved in substrate recognition were studied by site-directed mutagenesis.
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Yamazawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Karin
authors.initials: K
authors.lastname: Mushiake
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ito
mesh_terms: D055162:Biocatalysis; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology*; D006715:Homoserine Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D006715:Homoserine Dehydrogenase