The Research Group of Ann McDermott Columbia University, Department of Chemistry

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Research Summary

NMR Structural Studies of Membrane Proteins: Most membrane-bound proteins are structurally uncharacterized at present; solid state NMR methods promise to offer important information for these systems. Recently we discovered that NMR spectra of uniformly labeled solid state proteins are well-resolved and may provide the basis for structural and functional studies. Many small proteins, including BPTI and ubiquitin, and several intrinsic membrane proteins have been studied using high-field state-of-the-art solid state NMR equipment. Torsional angles and tertiary contacts are characterized through existing dipolar methods.

Enzymes, Hydrogen Bonding Geometry, and Dynamics: For most enzymes and drug targets, ligand binding is associated with the motion of a flexible loop or domain and the restructuring of hydrogen bonds and other contacts. The characteristic timescales of an active-site flexible loop in TIM is under investigation. Similarly, metal-substrate geometry as well as conformational exchange rates are studied for metalloenzymes, such as the important drug target cytochrome P450. NMR measurements in the active sites of enzymes give insight into catalytic mechanism, drug binding modes, and dynamics.

NMR Methods Development, Enhanced Signals, and Alignment Protocols: NMR signals associated with the photosynthetic apparatus appear with intensities enhanced 300 to 1,000 times, relative to control values. We have proposed a mechanism for this remarkable effect and achieved quantitative agreement. We have demonstrated alignment of liquids in the presence of large AC electric fields, as detected by NMR spectroscopy. This experiment benefits simultaneously from the advantages of NMR for studying both solids and liquids. Ongoing design and optimization of NMR hardware for these and other applications is a central activity in our research group.

McDermott: Chemistry Department