title: Identification of a Highly Conserved Hypothetical Protein TON_0340 as a Probable Manganese-Dependent Phosphatase.
abstract: A hypothetical protein TON_0340 of a Thermococcus species is a protein conserved in a variety of organisms including human. Herein, we present four different crystal structures of TON_0340, leading to the identification of an active-site cavity harboring a metal-binding site composed of six invariant aspartate and glutamate residues that coordinate one to three metal ions. Biochemical and mutational analyses involving many phosphorous compounds show that TON_0340 is a Mn2+-dependent phosphatase. Mg2+ binds to TON_0340 less tightly and activates the phosphatase activity less efficiently than Mn2+. Whereas Ca2+ and Zn2+ are able to bind to the protein, they are unable to activate its enzymatic activity. Since the active-site cavity is small and largely composed of nearly invariant stretches of 11 or 13 amino acids, the physiological substrates of TON_0340 and its homologues are likely to be a small and the same molecule. The Mn2+-bound TON_0340 structure provides a canonical model for the ubiquitously present TON_0340 homologues and lays a strong foundation for the elucidation of their substrate and biological function.
authors.affiliation: Department of Biological Sciences, KAIST Institute for the Biocentury, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Young-Sik
authors.initials: YS
authors.lastname: Sohn
authors.affiliation: Department of Biological Sciences, KAIST Institute for the Biocentury, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Seong-Gyu
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, KAIST Institute for the Biocentury, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Kwang-Hoon
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
authors.forename: Bonsu
authors.initials: B
authors.lastname: Ku
authors.affiliation: Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
authors.forename: Ho-Chul
authors.initials: HC
authors.lastname: Shin
authors.affiliation: Department of Chemistry and Nano Science, Ewha Womans University, Seoul, Korea.
authors.forename: Sun-Shin
authors.initials: SS
authors.lastname: Cha
authors.affiliation: Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang, Kyungbuk, Korea.
authors.forename: Yeon-Gil
authors.initials: YG
authors.lastname: Kim
authors.affiliation: Marine Biotechnology Research Center, Korea Institute of Ocean Science & Technology, Ansan, Korea.
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Marine Biotechnology Research Center, Korea Institute of Ocean Science & Technology, Ansan, Korea.
authors.forename: Sung-Gyun
authors.initials: SG
authors.lastname: Kang
authors.affiliation: Department of Biological Sciences, KAIST Institute for the Biocentury, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
authors.forename: Byung-Ha
authors.initials: BH
authors.lastname: Oh
mesh_terms: D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008345:Manganese / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010749:Phosphoprotein Phosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D019712:Thermococcus / Q000737:chemistry* / Q000201:enzymology
chemical_list: D019843:Archaeal Proteins; D011994:Recombinant Proteins; D008345:Manganese; D010749:Phosphoprotein Phosphatases