David A. Johnson
Professor of Biomedical Sciences
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Physical Biochemistry Signal Transduction
Ph.D., University of California, San Francisco, 1978
VOICE: 951-827-3831 |
Quantitative Fluorescence Spectroscopic Analysis of Protein Structure and Dynamics. The central focus of the laboratory is toward the development and the use of primarily quantitative fluorescence spectroscopic methods to understand at a molecular level how drugs and proteins work. Four systems are currently being examined: the acetylcholine binding protein (AcChBP), cAMP dependent protein kinase (PKA), acetylcholinesterase (AcChE), and protease-activated kinase 2 (Pak2). Specific objectives include: (i) determination of the dynamic linkages between subdomains of the AcChBP, (ii) spatial and temporal mapping of the interface between the catalytic and regulatory subunits of PKA, (iii) determination of the time-course of regulatory subunit conformational changes associated with binding to and dissociation form the catalytic subunit of PKA, (iv) assessment of the functional significance of ligand-induced changes in subdomain flexibility of AcChE, and (v) determination of the molecular basis of GTP-dependent and GTP-independent regulation of Pak2.
SELECTED PUBLICATIONS
Yang, S., Fletcher, W. H., and Johnson, D. A. , 1995. Regulation of cAMP-dependent protein kinase: Enzyme activation without dissociation. Biochemistry 34, 6267-6271.
Johnson, D. A. and Ayres, S. 1996. Quinacrine noncompetitive inhibitor binding site localized on the nicotinic acetylcholine receptor in the open state. Biochemistry 35, 6330-6336.
Gangal, M., Cox, S., Lew, J., Clifford, T., Garrod, S. M., Aschbaher, M., Taylor, S. S., and Johnson, D. A. 1998. Backbone Flexibility of Five Sites on the Catalytic Subunit of cAMP-Dependent Protein Kinase in the Open and Closed Conformations. Biochemistry 37, 13728-35.
Hauer, J. A. Taylor, S. S., & Johnson, D.A. 1999. Binding-Dependent Disorder-Order Transition in PKI": A Fluorescence Anisotropy Study. Biochemistry 38, 6774-6780.
Gangal, M., Clifford, T., Deich, J., Cheng, X., Taylor, S. S., and Johnson, D. A. 1999. Mobilization of the A-Kinase Through an Isoform-Specific Intermolecular Switch. PNAS 96, 12394-12399.
Li, F., Gangal, M., Jones, J.M., Deich, J., Lovett, K.E., Taylor , S.S., and Yang, S., Rogers, K. M., and Johnson, D. A . 2005 MgATP-induced conformational change of the catalytic subunit of cAMP-dependent protein kinase. Biophysical Chemistry 113 , 93-99. 2000. Consequences of cAMP and Catalytic-Subunit Binding on the Flexibility of the A-Kinase Regulatory Subunit. Biochemistry 39, 15626-15632.
Johnson, D. A., Akamine, P., Radzio-Andelm, E., Madhusdan, and Taylor , S. S. 2001. Dynamics of cAMP-Dependent Protein Kinase, ACS Reviews 101, 2243-2270.
Li, F., Gangal, M., Jones, J.M., Deich, J., Lovett, K.E., Taylor , S.S., and Johnson, D. A. 2000. Consequences of cAMP and Catalytic-Subunit Binding on the Flexibility of the A-Kinase Regulatory Subunit. Biochemistry 39, 15626-15632.
Shi, J., Tai, K., McCammon, J.A., Taylor, P., and Johnson, D. A. 2003 Nanosecond Dynamics of the Mouse Acetylcholinesterase Cys69-Cys96 Omega Loop, 2003 J. Biol. Chem. 33, 30905-30911.
Boyd, A. E., Dunlop, C. S., Marnett, A. B., Wong, L., Taylor, P., and Johnson, D. A . 2004 Nanosecond Dynamics of the Mouse Acetylcholinesterase near the Active-Site Gorge, J. Biol. Chem. 279, 26612-26618.
Yang, S., Rogers, K. M., and Johnson, D. A . 2005 MgATP-induced conformational change of the catalytic subunit of cAMP-dependent protein kinase. Biophysical Chemistry 113, 93-99.
Tan, D. Johnson, D. A. , Wu, W., Zeng, L., Chen, Y. H., Chen, W. Y., Vonderhaar, B. K., and Walker, A. M. 2005. Unmodified Prolactin (PRL) and S179D PRL-initiated Bioluminescence Resonance Energy Transfer between Homo- and Hetero-pairs of Long and Short Human Prolactin Receptors in Living Human Cells. Molecular Endocrinology 19, 1291-1303.
Johnson, D.A. 2005. C-Terminus of a Long a-Neurotoxin Is Highly Mobile When Bound to the Nicotinic Acetylcholine Receptor: A Time-Resolved Fluorescence Anisotropy Approach. Biophysical Chemistry 116, 213-218.