Crystal structure of a peptidoglycan glycosyltransferase suggests a model for processive glycan chain synthesis.
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 beta-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-A 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 lambda-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.
Yuan
Yanqiu
Y
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Barrett
Dianah
D
Zhang
Yi
Y
Kahne
Daniel
D
Sliz
Piotr
P
Walker
Suzanne
S
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D016695:Glycosyltransferases / Q000737:chemistry*; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010457:Peptidoglycan / Q000737:chemistry*; D046928:Peptidoglycan Glycosyltransferase / Q000737:chemistry* / Q000502:physiology; D011134:Polysaccharides / Q000737:chemistry*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D010457:Peptidoglycan; D011134:Polysaccharides; D016695:Glycosyltransferases; D046928:Peptidoglycan Glycosyltransferase