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Professor of Biochemistry

Investigator, HHMI


Education
1988 - BS Biochemistry, Martin-Luther University of Halle, Germany
1989 - MS Biochemistry, Martin-Luther University of Halle, Germany
1994 - PhD Biochemistry, Martin-Luther University of Halle, Germany
1998 - Postdoc Structural Biology, Dept. of Chemistry, University of California, Berkeley & Structural Biology Division, Lawrence Berkeley National Laboratory

Contact
Email: dkern @ brandeis.edu
Office: Volen 444
Dept. of Biochemistry, MS 009
Brandeis University
415 South Street
Waltham, MA 02454, USA
Phone: (781) 736-2354 Fax: (781) 736-2316
Website:Life Sciences Faculty at Brandeis

Dorothee Kern, PhD


Research Interests

Motions are the basis for the function of biological macromolecules. Whereas for many enzymes the structures have been solved, very little is known about dynamic processes, which trigger catalysis. Our main goal is to characterize these motions in enzymes to provide a better understanding of the atomic events in enzyme catalysis as a function of time. We use NMR as a primary tool because it is an excellent method to measure dynamic processes ranging from picoseconds to days. We complement our experiments by computational techniques, namely, molecular dynamics simulations, which provide atomistic insight into the dynamics of macromolecules. Our aim is to reveal the physical mechanism of transitions by combining experimental to computational methods. Our current work is focused on following topics:

  1. Analysis the kinetics of reversible enzyme reactions.
  2. Unraveling activation mechanism of two-component regulatory systems
  3. Observing the dynamics and conformational transitions of enzymes in atomic details.

More ...


Selected Publications

Renee Otten, Janice Villali, Dorothee Kern, and Frans A. A. Mulder. Probing Microsecond Time Scale Dynamics in Proteins by Methyl 1H Carr−Purcell−Meiboom−Gill Relaxation Dispersion NMR Measurements. Application to Activation of the Signaling Protein NtrCr. J. Am. Chem. Soc., In Press, Nov 2010.

Janice Villali and Dorothee Kern. Choreographing an enzyme's dance. Curr Opin Chem Biol, 14(5):636-643, Oct 2010.

Alexandra K Gardino, Janice Villali, Aleksandr Kivenson, Ming Lei, Ce Feng Liu, Phillip Steindel, Elan Z Eisenmesser, Wladimir Labeikovsky, Magnus Wolf-Watz, Michael W Clarkson, and Dorothee Kern. Transient non-native hydrogen bonds promote activation of a signaling protein. Cell, 139(6):1109–1118, Dec 2009.

James S Fraser, Michael W Clarkson, Sheena C Degnan, Renske Erion, Dorothee Kern, and Tom Alber. Hidden alternative structures of proline isomerase essential for catalysis. Nature, 462(7273):669–673, Dec 2009.

Katherine Henzler-Wildman and Dorothee Kern. Dynamic personalities of proteins. Nature, 450(7172):964–972, Dec 2007.

Katherine A Henzler-Wildman, Ming Lei, Vu Thai, S. Jordan Kerns, Martin Karplus, and Dorothee Kern. A hierarchy of timescales in protein dynamics is linked to enzyme catalysis. Nature, 450(7171):913–916, Dec 2007.

Katherine A Henzler-Wildman, Vu Thai, Ming Lei, Maria Ott, Magnus Wolf-Watz, Tim Fenn, Ed Pozharski, Mark A Wilson, Gregory A Petsko, Martin Karplus, Christian G Hbner, and Dorothee Kern. Intrinsic motions along an enzymatic reaction trajectory. Nature, 450(7171):838–844, Dec 2007.

Elan Z Eisenmesser, Oscar Millet, Wladimir Labeikovsky, Dmitry M Korzhnev, Magnus Wolf-Watz, Daryl A Bosco, Jac J Skalicky, Lews E Kay, and Dorothee Kern. Intrinsic dynamics of an enzyme underlies catalysis. Nature, 438(7064):117–121, Nov 2005.

Magnus Wolf-Watz, Vu Thai, Katherine Henzler-Wildman, Georgia Hadjipavlou, Elan Z Eisenmesser, and Dorothee Kern. Linkage between dynamics and catalysis in a thermophilic-mesophilic enzyme pair. Nat Struct Mol Biol, 11(10):945–949, Oct 2004.

Daryl A Bosco, Elan Z Eisenmesser, Susan Pochapsky, Wesley I Sundquist, and Dorothee Kern. Catalysis of cis/trans isomerization in native hiv-1 capsid by human cyclophilin a. Proc Natl Acad Sci U S A, 99(8):5247–5252, Apr 2002.

Elan Zohar Eisenmesser, Daryl A Bosco, Mikael Akke, and Dorothee Kern. Enzyme dynamics during catalysis. Science, 295(5559):1520–1523, Feb 2002.

Brian F. Volkman, Doron Lipson, David E. Wemmer and Dorothee Kern Two-State Allosteric Behavior in a Single-Domain Signaling Protein. Science, 291:2429-2433, Mar 2001.

Dorothee Kern, Brian F. Volkman, Peter Luginbüh, Michael J. Nohail, Sydney Kust and David E. Wemme Structure of a transiently phosphorylated "switch" in bacterial signal transduction. Nature, 402:894-898, Dec 1999.

Dorothee Kern, Gunther Kern, Holger Neef, Kai Tittmann, Margrit Killenberg-Jabs, Christer Wikner, Gunter Schneider and Gerhard Hüber How thiamin diphosphate is activated in enzymes. Science, 275:67-70, Jan 1997.

Full List in Publications

Publication List on PubMed