title: Crystal structure of phosphopantothenate synthetase from Thermococcus kodakarensis.
abstract: Bacteria/eukaryotes share a common pathway for coenzyme A biosynthesis which involves two enzymes to convert pantoate to 4'-phosphopantothenate. These two enzymes are absent in almost all archaea. Recently, it was reported that two novel enzymes, pantoate kinase, and phosphopantothenate synthetase (PPS), are responsible for this conversion in archaea. Here, we report the crystal structure of PPS from the hyperthermophilic archaeon, Thermococcus kodakarensis and its complexes with substrates, ATP, and ATP and 4-phosphopantoate. PPS forms an asymmetric homodimer, in which two monomers composing a dimer, deviated from the exact twofold symmetry, displaying 4°-13° distortion. The structural features are consistent with the mutagenesis data and the results of biochemical experiments previously reported. Based on these structures, we discuss the catalytic mechanism by which PPS produces phosphopantoyl adenylate, which is thought to be a reaction intermediate.
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Kishimoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Kita
authors.forename: Takuya
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Hiroya
authors.initials: H
authors.lastname: Tomita
authors.forename: Yuusuke
authors.initials: Y
authors.lastname: Yokooji
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Imanaka
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Atomi
authors.forename: Kunio
authors.initials: K
authors.lastname: Miki
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D001665:Binding Sites; D003065:Coenzyme A / Q000096:biosynthesis; D018360:Crystallography, X-Ray; D046912:Multiprotein Complexes / Q000737:chemistry; D010204:Pantetheine / Q000031:analogs & derivatives / Q000378:metabolism; D010453:Peptide Synthases / Q000737:chemistry* / Q000648:ultrastructure*; D016415:Sequence Alignment; D019712:Thermococcus / Q000201:enzymology*
chemical_list: D019843:Archaeal Proteins; D046912:Multiprotein Complexes; D010204:Pantetheine; D000255:Adenosine Triphosphate; D010453:Peptide Synthases; C022374:phosphopantothenoyl-cysteine synthetase; C003129:4'-phosphopantetheine; D003065:Coenzyme A
keywords: CoA biosynthesis; archaea; asymmetrical homodimer; crystal structure; phosphopantothenate synthetase