title: Three-dimensional structure of a new enzyme, O-phosphoserine sulfhydrylase, involved in l-cysteine biosynthesis by a hyperthermophilic archaeon, Aeropyrum pernix K1, at 2.0A resolution.
abstract: O-Phosphoserine sulfhydrylase is a new enzyme found in a hyperthermophilic archaeon, Aeropyrum pernix K1. This enzyme catalyzes a novel cysteine synthetic reaction from O-phospho-l-serine and sulfide. The crystal structure of the enzyme was determined at 2.0A resolution using the method of multi-wavelength anomalous dispersion. A monomer consists of three domains, including an N-terminal domain with a new alpha/beta fold. The topology folds of the middle and C-terminal domains were similar to those of the O-acetylserine sulfhydrylase-A from Salmonella typhimurium and the cystathionine beta-synthase from human. The cofactor, pyridoxal 5'-phosphate, is bound in a cleft between the middle and C-terminal domains through a covalent linkage to Lys127. Based on the structure determined, O-phospho-l-serine could be rationally modeled into the active site of the enzyme. An enzyme-substrate complex model and a mutation experiment revealed that Arg297, unique to hyperthermophilic archaea, is one of the most crucial residues for O-phosphoserine sulfhydrylation activity. There are more hydrophobic areas and less electric charges at the dimer interface, compared to the S.typhimurium O-acetylserine sulfhydrylase.
authors: Research Institute for Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST, Kansai), 1-8-31, Midorigaoka, Ikeda, Osaka 563-8577, Japan.
authors: Yutaka
authors: Y
authors: Oda
authors: Koshiki
authors: K
authors: Mino
authors: Kazuhiko
authors: K
authors: Ishikawa
authors: Mitsuo
authors: M
authors: Ataka
mesh_terms: D041522:Aeropyrum / Q000378:metabolism*; D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry; D001665:Binding Sites; D019757:Carbon-Oxygen Lyases / Q000737:chemistry*; D002384:Catalysis; D018360:Crystallography, X-Ray; D003541:Cystathionine beta-Synthase / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry*; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012486:Salmonella typhimurium / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013053:Spectrophotometry
chemical_list: D001120:Arginine; C503351:O-phosphoserine sulfhydrylase, Aeropyrum pernix; D019757:Carbon-Oxygen Lyases; D003541:Cystathionine beta-Synthase; D003545:Cysteine