|Title||Structural analysis of the sialyltransferase CstII from Campylobacter jejuni in complex with a substrate analog|
|Publication Type||Journal Article|
|Year of Publication||2004|
|Authors||Chiu, CPC, Watts, AG, Lairson, LL, Gilbert, M, Lim, D, WAKARCHUK, WW, Withers, SG, Strynadka, NCJ|
|Journal||NATURE STRUCTURAL & MOLECULAR BIOLOGY|
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.