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Structural analysis of the sialyltransferase CstII from Campylobacter jejuni in complex with a substrate analog

TitleStructural analysis of the sialyltransferase CstII from Campylobacter jejuni in complex with a substrate analog
Publication TypeJournal Article
Year of Publication2004
AuthorsChiu, CPC, Watts, AG, Lairson, LL, Gilbert, M, Lim, D, WAKARCHUK, WW, Withers, SG, Strynadka, NCJ
JournalNATURE STRUCTURAL & MOLECULAR BIOLOGY
Volume11
Pagination163-170
Date PublishedFEB
ISSN1545-9985
Abstract

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.

DOI10.1038/nsmb720