SCIENCE AT THE EDGE SEMINAR
http://www.pa.msu.edu/seminars/edge

11:30 A.M., Friday, November 1, 2002

Room 1400 Biomedical and Physical Sciences Building

Refreshments served at 11:15

Speaker:  Dorothee  Kern
          Department of Biochemistry
          Brandeis University, Waltham, MA

Title:    Enzymes in Action in the NMR Tube: 
          Protein Dynamics During Catalysis and Signaling

Abstract: 

A fundamental challenge for understanding protein function is the
characterization of proteins as dynamic objects. In this talk I will
present new experimental approaches to go beyond static structures with
the ultimate goal to "see" macromolecules reacting at atomic resolution.
Nuclear magnetic resonance spectroscopy, a technique that is based on the
spin properties of different nuclei, is used not only to determine
structures of proteins, but to look to the "dynamic hotspots"
in these structures. Modern spin relaxation experiments on many atoms
within the protein allow a quantitative analysis of the dynamics. We have
developed methods that allow measurements of dynamics in enzymes in
action. With this technique dynamics can be linked to function as
demonstrated on two examples, the activation of a signaling protein (1)
and the dynamic behavior of an enzyme during turnover (2). The
experimental results clearly reveal collective motions that are
correlated to the chemical steps of substrate turnover. Finally NMR
relaxation experiments are applied to exploit the mechanism of HIV
virulence promotion by the human enzyme CypA.

The presented experiments demonstrate how physical techniques applied to
biological systems advance our fundamental understanding of complex
biological molecules such as proteins which consists of several thousand
atoms.


References:

Volkman, B., Lipson, D., Wemmer, D. and Kern, D.
"Two-state allosteric behavior in a single domain signaling
protein" (2001) Science, 291, 2429-2433

Eisenmesser, E. Z., Bosco, D. A., Akke, M. and Kern, D.
"Enzyme Dynamics During Catalysis" Science 295, 1520-1523 (2002)

Bosco,D.A., Eisenmesser, E.Z., Pochapsky, S., Sundquist, W.I. and Kern, D.
"Catalysis of cis/trans isomerization in native HIV-1 capsid by human
cyclophilin A" Proc. Natl. Acad. Sci. USA, 99(8), 5247-5252 (2002)


*This work is supported by NIH.