A major goal of much biomedical research is to understand how various proteins function. One approach toward this goal is to study the structure of these proteins in the hope that understanding the structures will provide clues about the function. While this has been a valuable approach, we note that protein structures change as the proteins carry out their function so that methods which can measure the dynamics of structural changes in biologically important molecules are very important. We have developed a technique which allows us to measure circular dichroism spectra, which are sensitive to macromolecular structure, with nanosecond time resolution. In this proposal we seek to renew funding for this project in order to extend the method to provide improved time-resolution in the far ultraviolet spectral region (an important spectral region for determining structures) and to apply the method to study a variety of biomedically important problems. These include studies of the function of heme proteins such as myoglobin and hemoglobin, studies of the function of phytochrome, a plant regulatory protein, studies of electron transfer processes in proteins, studies of proteins affecting muscle contractions, and studies of protein folding processes in both model peptide systems and natural proteins.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Molecular and Cellular Biophysics Study Section (BBCA)
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University of California Santa Cruz
Schools of Arts and Sciences
Santa Cruz
United States
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Goldbeck, R A; Thomas, Y G; Chen, E et al. (1999) Multiple pathways on a protein-folding energy landscape: kinetic evidence. Proc Natl Acad Sci U S A 96:2782-7
Chen, E; Wood, M J; Fink, A L et al. (1998) Time-resolved circular dichroism studies of protein folding intermediates of cytochrome c. Biochemistry 37:5589-98
Chen, E; Lapko, V N; Song, P S et al. (1997) Dynamics of the N-terminal alpha-helix unfolding in the photoreversion reaction of phytochrome A. Biochemistry 36:4903-8
Goldbeck, R A; Sagle, L; Kim-Shapiro, D B et al. (1997) Evidence for heme-heme excitonic coupling in the Soret circular dichroism of hemoglobin. Biochem Biophys Res Commun 235:610-4
Chen, E; Goldbeck, R A; Kliger, D S (1997) Nanosecond time-resolved spectroscopy of biomolecular processes. Annu Rev Biophys Biomol Struct 26:327-55
Goldbeck, R A; Kim-Shapiro, D B; Kliger, D S (1997) Fast natural and magnetic circular dichroism spectroscopy. Annu Rev Phys Chem 48:453-79
Chen, E; Lapko, V N; Lewis, J W et al. (1996) Mechanism of native oat phytochrome photoreversion: a time-resolved absorption investigation. Biochemistry 35:843-50
Bjorling, S C; Goldbeck, R A; Paquette, S J et al. (1996) Allosteric intermediates in hemoglobin. 1. Nanosecond time-resolved circular dichroism spectroscopy. Biochemistry 35:8619-27
Goldbeck, R A; Paquette, S J; Bjorling, S C et al. (1996) Allosteric intermediates in hemoglobin. 2. Kinetic modeling of HbCO photolysis. Biochemistry 35:8628-39
Shapiro, D B; Esquerra, R M; Goldbeck, R A et al. (1996) A study of the mechanisms of slow religation to sickle cell hemoglobin polymers following laser photolysis. J Mol Biol 259:947-56

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