Professor of Chemistry and Chemical Biology and of Biological Chemistry and Molecular Pharmacology Co-Director, Chemical Biology PhD Program
12 Oxford Street
Cambridge, MA 02138
Lab Size: Greater than 10
For many years our research group has been interested in the mechanisms of various antibiotics that kill Gram-negative bacteria and the fundamental cellular processes they inhibit. We have primarily focused on drugs that target bacterial cell wall biosynthesis, including the beta-lactams, vancomycin, and moenomycin. We use these molecules to study the protein machines that synthesize and degrade the bacterial cell wall. Because we are interested in antibiotics that kill Gram-negative organisms by targeting their cell envelope, we are also interested in how the structure of the outer membrane is established and maintained. This is a stereochemical problem since biological membranes are asymmetric and require proper spatial organization of their constituent lipids and proteins in order to function correctly. The assembly of this organellar membrane must be accomplished outside the cell in the absence of an obvious energy source. Our research focuses on two multi-protein complexes that are involved in assembling membrane proteins and lipopolysaccharide. We want to understand how the different components of these machines function in the proper assembly of this membrane barrier as well as the mechanisms that lead to defects.
S. Okuda, E. Freinkman, D. Kahne. Cytoplasmic ATP hydrolysis powers transport of lipopolysaccharide across the periplasm in E. coli. Science 2012; 338:1214-7.
S.S. Chng, M. Xue, R.A. Garner, H. Kadokura, D. Boyd, J. Beckwith, D. Kahne. Disulfide rearrangement triggered by translocon assembly controls lipopolysaccharide export. Science 2012; 337:1665-8.
C.L. Hagan, S. Kim, D. Kahne. Reconstitution of outer membrane protein assembly from purified components. Science 2010; 328:890-2.
S. Kim, J.C. Malinverni, P. Sliz, T.J. Silhavy, S.C. Harrison, D. Kahne. Structure and function of an essential component of the outer membrane protein assembly machine. Science 2007; 317:961-964.
T. Wu, J. Malinverni, N. Ruiz, S. Kim, T.J. Silhavy, D. Kahne. Identification of a multi-component complex required for outer membrane biogenesis in Escerichia coli. Cell 2005; 121:235-246.