title: Structural analysis of sialyltransferase PM0188 from Pasteurella multocida complexed with donor analogue and acceptor sugar.
abstract: PM0188 is a newly identified sialyltransferase from P. multocida which transfers sialic acid from cytidine 5'-monophosphonuraminic acid (CMP-NeuAc) to an acceptor sugar. Although sialyltransferases are involved in important biological functions like cell-cell recognition, cell differentiation and receptor-ligand interactions, little is known about their catalytic mechanism. Here, we report the X-ray crystal structures of PM0188 in the presence of an acceptor sugar and a donor sugar analogue, revealing the precise mechanism of sialic acid transfer. Site-directed mutagenesis, kinetic assays, and structural analysis show that Asp141, His311, Glu338, Ser355 and Ser356 are important catalytic residues; Asp141 is especially crucial as it acts as a general base. These complex structures provide insights into the mechanism of sialyltransferases and the structure-based design of specific inhibitors.
authors.affiliation: Department of Biology and Protein Network Research Center, Yonsei University, Seoul, Korea.
authors.forename: Dong-Uk
authors.initials: DU
authors.lastname: Kim
authors.forename: Ji-Ho
authors.initials: JH
authors.lastname: Yoo
authors.forename: Yong Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Kim
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Cho
mesh_terms: D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry*; D002384:Catalysis; D018360:Crystallography, X-Ray; D007700:Kinetics; D008958:Models, Molecular; D009438:Neuraminic Acids / Q000737:chemistry; D016979:Pasteurella multocida / Q000201:enzymology*; D017434:Protein Structure, Tertiary; D012799:Sialyltransferases / Q000737:chemistry*
chemical_list: D002241:Carbohydrates; D009438:Neuraminic Acids; D012799:Sialyltransferases