Assistant Professor
Department of Chemistry
Krieger School of Arts & Sciences

jtolman@jhu.edu

239 Remsen Hall
3400 N. Charles Street
Baltimore, MD 21218

Office: 410-516-8022

Research in my lab is concerned with both the development and application of novel NMR techniques for studying the complex interactions that underlie biological function. Of particular interest are studies of molecular dynamics, the nature of intermolecular recognition and the quaternary organization of multi-domain protein systems. Although the full repertoire of multidimensional NMR methodology is employed to study these problems, an emphasis is placed on recently developed techniques for the measurement of Residual Dipolar Couplings (RDCs) in macromolecules. These RDCs, which are normally averaged to zero in solution, are made observable by introducing a very weak degree of alignment of the biomolecule relative to the magnetic field. The resulting RDCs are relatively easily measured and represent an abundant source of highly precise information on the relative orientations of different internuclear ‘bonds’ within the molecule. In addition, RDCs exhibit sensitivity to molecular motions on the nsec-msec timescales, during which many functionally important motions occur. An ongoing effort is to develop effective experimental as well as analytical tools for the characterization of biomolecular motions at atomic resolution.

A more applied focus of the laboratory is the NMR spectroscopic structural investigation of aspects of the ubiquitin-proteasome protein degradation pathway. Proteins are targeted for proteasmonal degradation by means of an attached poly-ubiquitin chain. The mechanism by which individual ubiquitin units are added to a protein substrate, ultimately destined for proteasomal degradation, is controlled by means of a complicated web of interactions among the many ubiquitin conjugating (E2) and ubiquitin ligase (E3) enzymes. A current project is to understand the structural mechanism for the recognition of human ubiquitin conjugating enzyme 7 (Ubc7) by its cognate E3, and how this recognition event serves to activate Ubc7’s catalytic role in producing ubiquitin-ubiquitin K48-G76 isopeptide linkages.

Selected Publications
Ruan, K., and J.R. Tolman. (2005) Composite alignment media for the measurement of independent sets of NMR residual dipolar couplings. J. Am. Chem. Soc. 127:15032-15033.

Tolman, J.R., and H.M. Al-Hashimi. (2003) NMR studies of biomolecular dynamics and structural plasticity using residual dipolar couplings. Ann. Reports NMR Spect. 51:105-166.

Briggman, K.B., and J.R. Tolman. (2003) De novo determination of bond orientations and order parameters from residual dipolar couplings with high accuracy. J. Am. Chem. Soc. 125:10164-10165.

Tolman, J.R. (2002) A novel approach to the retrieval of structural and dynamic information from residual dipolar couplings using several oriented media in biomolecular NMR spectroscopy. J. Am. Chem. Soc. 124:12020-12030.

Tolman, J.R. (2001) Dipolar couplings as a probe of molecular dynamics and structure in solution. Curr. Opin. Struct. Biol. 11:532-539.

Tolman, J.R., J.M. Flanagan, M.A. Kennedy, and J.H. Prestegard. (1997) NMR evidence for slow collective motions in cyanometmyoglobin. Nat. Struct. Biol. 4:292-297.