Molecular structure of alpha-D-glucose-1-phosphate cytidylyltransferase from Salmonella typhi.
Dideoxysugars, which display biological activities ranging from mediating cell-cell interactions to serving as components in some antibiotics, are synthesized in various organisms via complex biochemical pathways that begin with the attachment of alpha-D-glucose 1-phosphate to either CTP or dTTP. Here we describe the three-dimensional structure of the alpha-D-glucose-1-phosphate cytidylyltransferase from Salmonella typhi, which catalyzes the first step in the production of CDP-tyvelose. For this investigation, the enzyme was crystallized in the presence of its product, CDP-glucose. In contrast to previous reports, the enzyme exists as a fully integrated hexamer with 32-point group symmetry. Each subunit displays a "bird-like" appearance with the "body" composed predominantly of a seven-stranded mixed beta-sheet and the two "wings" formed by beta-hairpin motifs. These two wings mediate subunit-subunit interactions along the 3-fold and 2-fold rotational axes, respectively. The six active sites of the hexamer are situated between the subunits related by the 2-fold rotational axes. CDP-glucose is anchored to the protein primarily by hydrogen bonds with backbone carbonyl oxygens and peptidic NH groups. The side chains of Arg111 and Asn188 from one subunit and Glu178 and Lys179 from the second subunit are also involved in hydrogen bonding with the ligand. The topology of the main core domain bears striking similarity to that observed for glucose-1-phosphate thymidylyltransferase and 4-diphosphocytidyl-2-C-methylerythritol synthetase.
Koropatkin
Nicole M
NM
Department of Biochemistry, University of Wisconsin, Madison 53706, USA.
Holden
Hazel M
HM
D000595:Amino Acid Sequence; D001665:Binding Sites; D002236:Carbohydrate Conformation; D005947:Glucose / Q000031:analogs & derivatives* / Q000737:chemistry; D016018:Least-Squares Analysis; D008958:Models, Molecular; D009702:Nucleoside Diphosphate Sugars / Q000737:chemistry; D009713:Nucleotidyltransferases / Q000737:chemistry*; D011487:Protein Conformation; D012485:Salmonella typhi / Q000201:enzymology*
D009702:Nucleoside Diphosphate Sugars; C073881:cytidine diphosphate-glucose; D009713:Nucleotidyltransferases; C020586:glucose-1-phosphate cytidylyltransferase; D005947:Glucose