| STRUCTURE |
Nature Structural & Molecular Biology 11, 163 - 170 (2004) Published online: 18 January 2004 | doi:10.1038/nsmb720 Structural analysis of the sialyltransferase CstII from Campylobacter jejuni in complex with a substrate analog Cecilia P C Chiu1, Andrew G Watts2, 4, Luke L Lairson2, 4, Michel Gilbert3, Daniel Lim1, Warren W Wakarchuk3, Stephen G Withers2 & Natalie C J Strynadka1 1 Department of Biochemistry and Molecular Biology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada. 2 Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada. 3 Institute for Biological Sciences, National Research Council, Room 3157, 100 Sussex Drive, Ottawa, Ontario K1A OR6, Canada. 4 These authors contributed equally to this work. Correspondence should be addressed to Natalie C J Strynadka natalie@byron.biochem.ubc.ca Sialic acid terminates oligosaccharide chains on mammalian and microbial cell surfaces, playing critical roles in recognition and adherence. The enzymes that transfer the sialic acid moiety from cytidine-5'-monophospho-N-acetyl-neuraminic acid (CMP-NeuAc) to the terminal positions of these key glycoconjugates are known as sialyltransferases. Despite their important biological roles, little is understood about the mechanism or molecular structure of these membrane-associated enzymes. We report the first structure of a sialyltransferase, that of CstII from Campylobacter jejuni, a highly prevalent foodborne pathogen. Our structural, mutagenesis and kinetic data provide support for a novel mode of substrate binding and glycosyl transfer mechanism, including essential roles of a histidine (general base) and two tyrosine residues (coordination of the phosphate leaving group). This work provides a framework for understanding the activity of several sialyltransferases, from bacterial to human, and for the structure-based design of specific inhibitors. |
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