Structural analysis of the sialyltransferase CstII from Campylobacter jejuni in complex with a substrate analog.
Nat Struct Mol Biol
; 11(2): 163-70, 2004 Feb.
Article
em En
| MEDLINE
| ID: mdl-14730352
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.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Sialiltransferases
/
Campylobacter jejuni
/
Ácido N-Acetilneuramínico do Monofosfato de Citidina
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article