title: Insights into trehalose synthesis provided by the structure of the retaining glucosyltransferase OtsA.
abstract: Trehalose is a nonreducing disaccharide that plays a major role in many organisms, most notably in survival and stress responses. In Mycobacterium tuberculosis, it plays a central role as the carbohydrate core of numerous immunogenic glycolipids including "cord factor" (trehalose 6,6'-dimycolate). The classical pathway for trehalose synthesis involves the condensation of UDP-glucose and glucose-6-phosphate to afford trehalose-6-phosphate, catalyzed by the retaining glycosyltransferase OtsA. The configurations of two anomeric positions are set simultaneously, resulting in the formation of a double glycoside. The three-dimensional structure of the Escherichia coli OtsA, in complex with both UDP and glucose-6-phosphate, reveals the active site at the interface of two beta/alpha/beta domains. The overall structure and the intimate details of the catalytic machinery reveal a striking similarity to glycogen phosphorylase, indicating a strong evolutionary link and suggesting a common catalytic mechanism.
authors.affiliation: Department of Chemistry, The University of York, York YO10 5YW, Heslington, United Kingdom.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Gibson
authors.forename: Johan P
authors.initials: JP
authors.lastname: Turkenburg
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Charnock
authors.forename: Ruth
authors.initials: R
authors.lastname: Lloyd
authors.forename: Gideon J
authors.initials: GJ
authors.lastname: Davies
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D005964:Glucosyltransferases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D006005:Phosphorylases / Q000737:chemistry; D011487:Protein Conformation; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D014199:Trehalose / Q000096:biosynthesis*
chemical_list: D014199:Trehalose; D005964:Glucosyltransferases; D006005:Phosphorylases; C023180:trehalose-6-phosphate synthase