Katherine A. Henzler-Wildman, Ph.D.
Assistant Professor
Biochemistry and Molecular Biophysics
Computational and Molecular Biophysics Program
Biochemistry Program
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Office Phone: 314-362-1674
Lab Phone: 314-362-1570
Other Phone:
FAX:
Box: 8231
Lab Address: 2808 North Building
Email: khenzler@WUSTL.EDU
Website: http://biochem.wustl.edu/~khenzler/
Keywords: membrane proteins; NMR; protein dynamics; transporters; multidrug resistance
Short Research Description: Functional importance of membrane protein dynamics |
Research Abstract:
Research in my laboratory is focused on the functional importance of membrane protein dynamics. To fully understand protein function, not only the structure, but the timescale, amplitude, and directionality of structural changes must be determined. The model system we are studying is the small multidrug resistance protein, EmrE, found in E. coli. We are interested in understanding how EmrE contributes to multidrug resistance: How is one transporter able to recognize and effectively transport a broad range of susbstrates?
As a secondary active transporter, EmrE uses coupled transport of one substrate down its electrochemical gradient (proton import) as the energy source to drive transport of a second substrate (polyaromatic cation export). Protein conformational change is required for proper function, allowing alternating access to either side of the membrane in response to substrate binding. Our research investigates the protein motions central to the transport process and the critical coupling between substrate binding and conformational interconversion.
We use a combination of biochemical and biophysical methods, but our primary tool in these studies is nuclear magnetic resonance spectroscopy (NMR). NMR offers a unique tool to study protein dynamics, since kinetic data is measured simultaneously with the chemical shift, a direct manifestation of atomic-resolution structure. By combining this data with traditional transport assays, we can determine the functional importance of the protein motions we observe. |
Selected Publications:
Henzler-Wildman KA and Kern D. Dynamic Personalities of Proteins. Nature 2007 450: 964-972.
Henzler-Wildman KA, Lei M, Thai V, Karplus M and Kern D. A Hierarchy of Timescales in Protein Dynamics Linked to Catalysis. Nature 2007 450: 913-916.
Henzler-Wildman KA, Thai V, Lei M, et al. Intrinsic Motions Along an Enzymatic Reaction Trajectory. Nature 2007 450: 838-844.
Wolf-Watz M, Thai V, Henzler-Wildman KA, et al. Linkage Between Dynamics and Catalysis in a Thermophilic-Mesophilic Enzyme Pair. Nat. Struct. Mol. Biol. 2004 11: 945-949.
Henzler Wildman KA, Martinez GV, Brown MF and Ramamoorthy A. Perturbation of the Hydrophobic Core of Lipid Bilayers by the Human Antimicrobial Peptide LL-37. Biochemistry 2004 438: 459-8469. |