Contact Information:

Dept. of Microbiology and
Molecular Genetics

Harvard Medical School

200 Longwood Ave.

Boston, MA 02115

phone: 617-432-5488

fax: 617-738-7664

suzanne_walker@hms.harvard.edu

Visit Dr. Walker's Website at CCB

Research Summary

The bacterial cell wall:  Most bacteria are surrounded by a heavily crosslinked polymer called peptidoglycan.  This polymer functions as an exoskeleton, helping to maintain cell shape and to stabilize the cell membrane so that it can withstand large internal osmotic pressure fluctuations.  Damage to the peptidoglycan layers results in bacterial cell death, making the biosynthesis of this polymer an important target for broad-spectrum antibiotics.  My laboratory is interested in the chemistry and biology of the extracellular enzymes involved in peptidoglycan biosynthesis.  We would like to understand how these extracellular enzymes function with one another and with key intracellular proteins involved in cell growth and division to make a complex, three-dimensional polymer from a simple disaccharide subunit on the cell surface.  We combine organic synthesis, enzymology, structural biology, fluorescence microscopy, and genetics to address problems related to the construction of the peptidoglycan layers and associated structures of the bacterial cell wall.    

Antibiotic discovery, mechanisms of action, and biosynthesis:  

We need new antibiotics to overcome antibiotic resistant bacterial infections.   My laboratory studies the mechanism of action and biosynthesis of potentially useful natural product antibiotics in the hope that a better understanding of how they function, combined with the ability to manipulate their structures, will lead to new drugs.  We also develop cell-based and in vitro strategies to discover inhibitors of potential therapeutic targets. 

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Selected Publications

Ostash B, Saghatelian A, and Walker S. A Streamlined Metabolic Pathway for the Biosynthesis of Moenomycin A, Chemistry and Biology, 2007;14:257-267.

Yuan Y, Barrett D, Zhang Y, Kahne D, Sliz P, and Walker S, Crystal structure of a peptidoglycan glycosyltransferase suggests a model for processive glycan chain synthesis, Proc Natl Acad Sci USA, 2007;104:5348-5353.

Tiyanont K, Doan T, Lazarus M, Fang X, Rudner D, and Walker S, Imaging peptidoglycan biosynthesis in Bacillus subtilis with fluorescent antibiotics, Proc. Natl. Acad. Sci. USA, 2006,103, 11033-11038.

Ginsberg C, Zhang Y-H, Yuan Y, and Walker S, In Vitro Reconstitution of Two Essential Steps in Wall Teichoic Acid Biosynthesis, ACS Chemical Biology, 2006, 1, 25-28.

Gross BJ, Kraybill BC, and Walker S, Discovery of O-GlcNAc transferase inhibitors, J. Am. Chem. Soc. 2005, 127, 14588-14589.

Lo M, Men H, Branstrom A, Helm J, Yao N, Goldman R, Walker S. A New Mechanism of Action Proposed for Ramoplanin. J. Am. Chem. Soc. 2000;122:3540-3541.

Ha S, Walker D, Shi Y, Walker S. The 1.9 Å crystal structure of E. coli MurG, a membrane-associated glycosyltransferase involved in peptidoglycan biosynthesis. Protein Science 2000;9:1045-1052.