Crystal structure of a peptidoglycan glycosyltransferase suggests a model for processive glycan chain synthesis

• Published in: Proceedings of the National Academy of Sciences - PNAS 2007-03, Vol.104 (13), p.5348-5353
• Main Authors: Yuan, Yanqiu, Barrett, Dianah, Zhang, Yi, Kahne, Daniel, Sliz, Piotr, Walker, Suzanne
• Format: Article
• Language: English
• Subjects: Active sites; Amino Acid Sequence; Animals; Antibiotics; Aquifex aeolicus; Bacterial Proteins - chemistry; Bacteriology; Binding Sites; Biochemistry; Biological Sciences; Carbohydrates; Catalysis; Cells; Chemical synthesis; Crystal structure; Crystallography, X-Ray; Dimers; Drug resistance; Enzymes; Glycosyltransferases - chemistry; Lipids; Models, Biological; Models, Molecular; Molecular Sequence Data; Molecules; Monomers; P branes; Peptidoglycan - chemistry; Peptidoglycan Glycosyltransferase - chemistry; Peptidoglycan Glycosyltransferase - physiology; Polymerization; Polymers; Polysaccharides; Polysaccharides - chemistry; Protein Conformation; Protein Structure, Tertiary; Proteins; Sequence Homology, Amino Acid
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0701160104

Peptidoglycan is an essential polymer that forms a protective shell around bacterial cell membranes. Peptidoglycan biosynthesis is the target of many clinically used antibiotics, including the β-lactams, imipenems, cephalosporins, and glycopeptides. Resistance to these and other antibiotics has prompted interest in an atomic-level understanding of the enzymes that make peptidoglycan. Representative structures have been reported for most of the enzymes in the pathway. Until now, however, there have been no structures of any peptidoglycan glycosyltransferases (also known as transglycosylases), which catalyze formation of the carbohydrate chains of peptidoglycan from disaccharide subunits on the bacterial cell surface. We report here the 2.1-Å crystal structure of the peptidoglycan glycosyltransferase (PGT) domain of Aquifex aeolicus PBP1A. The structure has a different fold from all other glycosyltransferase structures reported to date, but it bears some resemblance to λ-lysozyme, an enzyme that degrades the carbohydrate chains of peptidoglycan. An analysis of the structure, combined with biochemical information showing that these enzymes are processive, suggests a model for glycan chain polymerization.