title: The crystal structure of a novel phosphopantothenate synthetase from the hyperthermophilic archaea, Thermococcus onnurineus NA1.
abstract: Pantothenate is the essential precursor of coenzyme A (CoA), a fundamental cofactor in all aspects of metabolism. In bacteria and eukaryotes, pantothenate synthetase (PS) catalyzes the last step in the pantothenate biosynthetic pathway, and pantothenate kinase (PanK) phosphorylates pantothenate for its entry into the CoA biosynthetic pathway. However, genes encoding PS and PanK have not been identified in archaeal genomes. Recently, a comparative genomic analysis and the identification and characterization of two novel archaea-specific enzymes show that archaeal pantoate kinase (PoK) and phosphopantothenate synthetase (PPS) represent counterparts to the PS/PanK pathway in bacteria and eukaryotes. The TON1374 protein from Thermococcus onnurineus NA1 is a PPS, that shares 54% sequence identity with the first reported archaeal PPS candidate, MM2281, from Methanosarcina mazei and 91% sequence identity with TK1686, the PPS from Thermococcus kodakarensis. Here, we report the apo and ATP-complex structures of TON1374 and discuss the substrate-binding mode and reaction mechanism.
authors.affiliation: Marine Biotechnology Research Division, Korea Institute of Ocean Science and Technology, Ansan 426-744, Republic of Korea.
authors.forename: Min-Kyu
authors.initials: MK
authors.lastname: Kim
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: An
authors.forename: Sun-Shin
authors.initials: SS
authors.lastname: Cha
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D007700:Kinetics; D010453:Peptide Synthases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000378:metabolism; D019712:Thermococcus / Q000201:enzymology* / Q000378:metabolism
chemical_list: D019843:Archaeal Proteins; D000255:Adenosine Triphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase; D010453:Peptide Synthases; C022318:pantothenate synthetase
keywords: Archaea; Coenzyme A biosynthesis; Crystal structure of TON1374; Crystal structure of TON1374/ATP complex; Phosphopantothenate synthetase