|Jerry C. Smith|
B.S. (1965): University of Mississippi
Ph.D. (1971) : University of North Carolina, Chapel Hill
Postdoc (1972) : Arizona State University
NIH Postdoctoral Fellowship & Re (1974) : University of Pennsylvania
Dr. Jerry C. Smith
Department of Chemistry
Georgia State University
P.O. Box 3965
Atlanta, Georgia 30302-3965
Department Office Phone: 404-413-5500
My research interests involve studies of the interaction of extrinsic, potential-sensitive molecular probes, anti-HIV, and anti-pneumocystis carinii drug candidate compounds with energy- transducing (mitochondrial) membranes. A project designed to evaluate the role of phospholipids in protein transport process(es) is also being developed. These research areas are described in turn below.
Extrinsic, potential-sensing probes are being employed in intact mitochondria and in submitochondrial particles (SMP) with the primary goal of assessing the kinetic competence of these probes, usually polyene dyes, to follow the time course of the membrane potential as it develops in response to substrate pulses in rapid mixing experiments. The use of microelectrodes or patch electrodes is not feasible for this purpose because the response time of the electrodes is too low and because of the small size of some of the mitochondrial preparations. The extent to which the probes can be calibrated with diffusion potentials and by null point titration procedures is also under study. The relative sensitive of the probes to surface vs transmembrane potentials is being assessed by development of probe location models using magnetic resonance techniques including NOESY spectroscopy and paramagnetic perturbants. Probe location models resulting from such work are being refined using molecular modeling computational techniques on probe-phospholipid bilayer complexes.
Potentially adverse effects resulting from the interaction of a number of pre-screened anti-HIV and anti-pneumocystis carinii drug candidate compounds with yeast and rat mitochondria or SMP are being characterized in terms of the effect of these compounds on electron transport, the energy coupling mechanism, the magnitude and time development of and pH as well as calcium transport. The site(s) of such interaction at the molecular level is being ascertained by isolation of respiratory chain components from mitochondria that have been exposed to these compounds. Of particular interest is the possible interaction of these drug candidates with the benzodiazepine receptor and other mitochondrial membrane channels.
The process(es) by which newly synthesized proteins are transported to their ultimate target cellular organelles is poorly understood. These proteins usually contain a leader or transit peptide that is crucial in realizing the transport process. The significance of the interaction of membrane phospholipids with these transit peptides in the protein translocation process will be explored by use of synthetically prepared transit peptide fragments in vesicles prepared from both high purity phospholipids and from extracts of organelle membranes, primarily chloroplasts. Circular dichroism and magnetic resonance techniques will be used in characterizing the structure of these peptide fragments and the extent to which this structure is changed upon their association with membranes. The resulting model of the location of the peptide in the bilayer will be refined using molecular modeling techniques. These studies are a collaboration with Professor William Nolan, Department of Biology, Georgia State University.
Smith, J.C., Chandrasekaran, S. & Strekowski, L.S. (1999). Interaction of the Probe Oxonol V and the Drug Candidate LS8 with Small Unilamellar DMPC Vesicles. Biophysical Journal, 76, A440.
Smith, J.C., & Chandrasekaran, S. (1998). The Locations of Potential-Sensitive Molecular Probes in DMPC Vesicles: An NMR Investigation. Biophysical Journal 74, A299.
Smith J.C., & Chandrasekaran S. (1997). Location Models for the Probe Oxonol V in 1,2-Dimyristoyl-sn-glycerol-3-phosphocholine(DMPC) Vesicles by NMR Spectroscopy. Biophysical Journal 72, WP443-WP443.
"The Effect of a Potential-Sensitive Barbituric-acid Molecular Probe on the Thermal Phase-Transition Properties of Multilamellar 1,2-Dimyristoyl-sn-glycero-3-phosphocholine Suspensions", Hamilton, D.; Gill, D. J.; Hopkins, H. P.; Nolan, W. G.; Smith, J. C. Chem. and Phys. Of Lipids, 1995, 75, 109-118.
"The Behavior of a Fast-Responding Barbituric Acid Potential-Sensitive Molecular Probe in Bovine Heart Submitrochondrial Particles", Tran, T. V.; Allen, S.; Smith, J.C. Biochim. Biophys. Acta, 1991, 1059, 265-274.
"NMR, Calorimetric, Spin-Label, and Optical Studies on a Trifluoromethyl-Substituted Syryl Molecular Probe in Dimysteroylphosphatidylcholine Vesicles and Multilamellar Suspensions: a Model for Location of Optical Probes", Bammel, B. P.; Hamilton, D. D.; Haughland, R. P.; Hopkins, H. P.; Schuette, J.; Szalecki, W.; Smith, J.C. Biochim. Biophys. Acta, 1990, 1024 61-81.
"The Effect of Extrinsic Potential-Sensitive Molecular Probes on the Thermal Phase Transition Properties of Dimysteroylphosphatidylcholine Model Membrane Preparations", Bammel, B.P.; Fumero, J.; Hopkins, H.P.; Smith, J. C. Biochim. Biophys. Acta, 1988 944, 164-176.