Bioanalytical Mass Spectrometry
Faculty Fellow, Associate Professor of Chemistry & Chemical Biology
The Barnett Institute
341 Mugar Life Sciences
Northeastern University
360 Huntington Avenue
Boston, MA 02115
email: j.engen@neu.edu
voice: 617-373-6046
fax: 617-373-2855
Engen Research Group Page>>
Chemistry Dept. Engen Page>>
Education
1994 B.S., Molecular Biology, Union College
1995 B.S., Biochemistry, Union College
1999 Ph.D., Analytical Chemistry, University of Nebraska-Lincoln
2000 EMBO Postdoctoral Fellow, EMBL Heidelberg, Germany
2001 Postdoctoral Associate, Los Alamos National Laboratory
Research Interests
Research in the laboratory centers on the use of state-of-the-art mass spectrometry (MS) to study the conformations and movements of proteins and protein machines. Mass spectrometry can be used to study protein conformation if the proteins in question are labeled with a structure-dependent labeling method such as amide hydrogen exchange (HX). See also www.hxms.com.
Proteins contain a number of hydrogens that can exchange with hydrogen in the surrounding solvent. The most useful hydrogen to follow is the backbone amide hydrogen. If the normal H2O solvent is changed to D2O, the protein gradually becomes deuterated. Because deuterium and hydrogen differ in mass by 1 dalton, the incorporation of deuterium (aka, hydrogen exchange) into a protein can be monitored with high resolution mass spectrometry.
The rate of HX depends on hydrogen bonding and solvent accessibility. Folded proteins can have amino acids with HX rates as much as 1 billion times slower than the same amino acid that is not in a folded protein. Protein folding and unfolding, whether in cells or in the test tube, represent large changes in protein structure, hydrogen bonding and solvent accessibility that can be investigated with HX MS. Smaller structural changes critical for protein function can also be probed with HX MS.
Projects of current interest include: (1) the analysis of structural changes in tyrosine kinases during interactions with regulatory proteins and (2) the analysis of the conformational features of viral proteins that are not amenable to crystallography or NMR.
There are ongoing opportunities for undergraduate, graduate and postdoctoral research in the group. Interested people should contact Prof. Engen by email.
Selected Recent Publications
Engen, J. R. (2009). Analysis of Protein Conformation and Dynamics by Hydrogen/Deuterium Exchange Mass Spectrometry. Anal. Chem. 81(19), Cover Feature.
Houde, D., Arndt, J., Domeier, W., Berkowitz, S. & Engen, J. R. (2009). Characterization of IgG1 conformation and conformational dynamics by hydrogen/deuterium exchange mass spectrometry. Anal. Chem. 81(7), 2644-2651.
Iacob, R. E., Dumitrescu, T. P., Zhang, J., Gray, N. S., Smithgall, T. E. & Engen, J. R. (2009). Conformational disturbance in Abl kinase upon mutation and deregulation. Proc. Natl. Acad. Sci. U.S.A. 106(5), 1386-1391.
Iacob, R. E., Murphy, J. P. 3rd & Engen, J. R. (2008). Ion mobility adds an additional dimension to mass spectrometry analysis of solution-phase hydrogen/deuterium exchange. Rapid Commun. Mass Spectrom. 22(18), 2898-2904.
Chen, S., Dumitrescu, T. P., Smithgall, T. E. & Engen, J. R. (2008). Abl N-terminal Cap stabilization of SH3 domain dynamics. Biochemistry 47(21), 5795-5803.
Wales, T. E., Fadgen, K. E., Gerhardt, G. C. & Engen, J. R. (2008). High-speed and high-resolution UPLC separation at zero degrees Celsius. Anal. Chem. 80(17), 6815-6820.
Engen, J. R., Wales, T. E., Hochrein, J. M., Meyn, M. A., Ozkam, S. B., Bahar, I. & Smithgall, T. E. (2008). Structure and dynamic regulation of Src-family kinases. Cell. Mol. Life Sci. 65(19), 3058-3073.
Mitchell, J. L. Trible, R. P., Emert-Sedlak, L. A., Weis, D. D., Lerner, E. C., Applen, J. J., Sefton, B. M., Smithgall, T. E. & Engen, J. R. (2007). Functional characterization and conformational analysis of the Herpesvirus saimiri Tip-C484 protein. J. Mol. Biol. 366(4), 1282-1293.
Trible, R. P., Emert-Sedlak, L., Wales, T. E., Ayyavoo, V., Engen, J. R., & Smithgall, T. E. (2007). Allosteric loss-of-function mutations in HIV-1 Nef from a Long-term Non-progressor. J. Mol. Biol. 374(1), 121-129.
Wales, T. E & Engen, J. R. (2006). Hydrogen exchange mass spectrometry for the analysis of protein dynamics. Mass Spectrom. Rev. 25(1), 158-170.
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