Department of Chemistry
3000 Broadway, MC 3113
New York, NY 10027
Dean of the Faculty office
309 Low: +1 212 854-3843
Chemistry Office: 212-854-8393
Chemistry Fax: 212-932-1289
 |
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.
 Back to Top |
Cytochrome P450 BM-3 in Complex with Its Substrate: Temperature-Dependent Spin State Equilibria in the Oxidized and Reduced States, Jovanovic T., Harris M., and McDermott A.E., App. Magn. Reson. 31 (3-4), 411-429 (2007)
Locating hydrogen atoms in single crystal and uniaxially aligned amino acids by solid-state NMR, Gross B. J., and McDermott A.E., J. Magn. Reson. 185, 12-18 (2007)
Substrate product equilibrium on a reversible enzyme, triosephosphate isomerase Rozovsky S., and McDermott A.E., Proc. Nat. Ac. Sci. 104, 2080-2085 (2007)
Filamentous phage studied by magic-angle spinning NMR: resonance assignment and secondary structure of the coat protein in Pf1, Goldbourt A., Gross B.J., Day L.D., and McDermott A.E., J. Am. Chem. Soc. 129(8), 2338-2344 (2007)
Conformational Dynamics of Substrate in the Active Site of Cytochrome P450 BM-3/NPG Complex: Insights from NMR Order Parameters, Ravindranathan K.P., Gallicchio E., Friesner R.A., McDermott A.E., and Levy R.M., J. Am. Chem. Soc. 129(3) 474-475 (2007)
Conformational Equilibrium of Cytochrome P450 BM-3 Complexed with N-Palmitoylglycine: A Replica Exchange Molecular Dynamics Study, Ravindranathan K.P, Gallicchio E., Friesner R.A., McDermott, A.E., and Levy R.M., J. Am. Chem. Soc. 128, 5786-5791 (2006)
Order parameters based on 13C1H, 13C1H2 and 13C1H3 heteronuclear dipolar powder patterns: a comparison of MAS-based solid-state NMR sequences, Lorieau J., McDermott, A.E., Magn. Reson. Chem. 44, 334-347 (2006)
Conformational Flexibility of a Microcrstaline Globular Protein: Order Parameters by Solid state NMR Spectroscopy, Lorieau J., McDermott, A.E., J. Am. Chem. Soc. 128(35), 11505-11512 (2006)
Observation of Ligand Binding to Cytochrome P450 BM-3 by Means of Solid-State NMR Spectroscopy, Jovanovic, T., McDermott, A.E., J. Am. Chem. Soc. 127, 13816 - 13821 (2005)
Thermal Equilibrium of High- and Low-Spin Forms of Cytochrome P450 BM-3: Repositioning of the Substrate? Jovanovic, T., Farid, R., Friesner, R. A., McDermott, A.E., J. Am. Chem. Soc. 127, 13548-13552 (2005)
| Back to Top |