Crystal structure of a peptidoglycan glycosyltransferase domain of a Class A penicillin binding protein

BIOL 189

Yanqiu Yuan, yyuan@fas.harvard.edu1, Dianah Barrett2, Yi Zhang3, Daniel E. Kahne, kahne@chemistry.harvard.edu3, Piotr Sliz4, and Suzanne Walker2. (1) Microbiology and Molecualr Genetics, Harvard Medical School, Boston, MA 02115, (2) Department of Microbiology and Molecular Genetics, Harvard Medical School, Armenise Bldg., Room 630, 200 Longwood Ave., Boston, MA 02115, (3) Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, (4) Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115
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. The 2.1-A crystal structure of the peptidoglycan glycosyltransferase (PGT) domain of Aquifex aeolicus PBP1A 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.
 

Frontiers in Chemical Biology
5:00 PM-7:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biological Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007