title: Structure of the dimeric form of CTP synthase from Sulfolobus solfataricus.
abstract: CTP synthase catalyzes the last committed step in de novo pyrimidine-nucleotide biosynthesis. Active CTP synthase is a tetrameric enzyme composed of a dimer of dimers. The tetramer is favoured in the presence of the substrate nucleotides ATP and UTP; when saturated with nucleotide, the tetramer completely dominates the oligomeric state of the enzyme. Furthermore, phosphorylation has been shown to regulate the oligomeric states of the enzymes from yeast and human. The crystal structure of a dimeric form of CTP synthase from Sulfolobus solfataricus has been determined at 2.5 Å resolution. A comparison of the dimeric interface with the intermolecular interfaces in the tetrameric structures of Thermus thermophilus CTP synthase and Escherichia coli CTP synthase shows that the dimeric interfaces are almost identical in the three systems. Residues that are involved in the tetramerization of S. solfataricus CTP synthase according to a structural alignment with the E. coli enzyme all have large thermal parameters in the dimeric form. Furthermore, they are seen to undergo substantial movement upon tetramerization.
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Iben
authors.initials: I
authors.lastname: Lauritsen
authors.forename: Martin
authors.initials: M
authors.lastname: Willemoës
authors.forename: Kaj Frank
authors.initials: KF
authors.lastname: Jensen
authors.forename: Eva
authors.initials: E
authors.lastname: Johansson
authors.forename: Pernille
authors.initials: P
authors.lastname: Harris
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001051:Apoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D017124:Conserved Sequence; D018360:Crystallography, X-Ray / Q000379:methods; D019281:Dimerization; D004926:Escherichia coli / Q000201:enzymology; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009711:Nucleotides / Q000096:biosynthesis; D010766:Phosphorylation; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D048229:Sulfolobus solfataricus / Q000201:enzymology*; D016963:Thermus thermophilus / Q000201:enzymology; D014544:Uridine Triphosphate / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D001051:Apoenzymes; D009711:Nucleotides; D021122:Protein Subunits; D014867:Water; D005973:Glutamine; D000255:Adenosine Triphosphate; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase; D014544:Uridine Triphosphate