title: Structure of the inositol-1-phosphate cytidylyltransferase from Thermotoga maritima.
abstract: The unique steps in the synthesis of an unusual osmolyte in hyperthermophiles, di-myo-inositol-1,1'-phosphate (DIP), involve the production of CDP-inositol and its condensation with an inositol-1-phosphate molecule to form phosphorylated DIP. While many organisms fuse both activities into a single enzyme, the two are separate in Thermotoga maritima. The crystal structure of the T. maritima inositol-1-phosphate cytidylyltransferase, which as a soluble protein may transiently associate with its membrane-embedded partner phospho-DIP synthase (P-DIPS), has now been obtained. The structure shows a conserved motif of sugar nucleotide transferases (COG1213) with a structurally reinforced C-terminal Cys bonded to the core of the protein. A bound arsenosugar identifies the location of the active site for inositol 1-phosphate. Based on homologous structures from several species and the identification of the crucial conserved aspartate residue, a catalytic mechanism for this enzyme is proposed as well as a mode for its association with P-DIPS. This structure imposes constraints on the mode of association, communication and temperature activation of two separate enzymes in T. maritima. For the first time, a working model for the membrane-bound P-DIPS unit has been constructed. This sheds light on the functioning of the phosphatidylserine and phosphatidylinositol synthases involved in many physiological processes that are homologous to P-DIPS. This work provides fresh insights into the synthesis of the unusual thermoprotective compound DIP in hyperthermophiles.
authors.affiliation: Sanford-Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Kurnasov
authors.forename: Hung-Jie Daniel
authors.initials: HJ
authors.lastname: Luk
authors.forename: Mary F
authors.initials: MF
authors.lastname: Roberts
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Stec
mesh_terms: D019916:Choline-Phosphate Cytidylyltransferase / Q000737:chemistry; D018360:Crystallography, X-Ray; D007295:Inositol Phosphates / Q000737:chemistry*; D009713:Nucleotidyltransferases / Q000737:chemistry*; D020124:Thermotoga maritima / Q000201:enzymology
chemical_list: D007295:Inositol Phosphates; C075843:di-myo-inositol-1,1'-phosphate; C002647:inositol 1-phosphate; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase
keywords: di-myo-inositol phosphate; inositol; inositol-1-phosphate citidylyltransferase