Michael A. Cusanovich
Regents Professor of Biochemistry
Professor of Chemistry
Vice President for Research and Graduate Studies Emeritus
Director of Arizona Research Laboratories
Ph.D. 1967, University of California, San Diego
Biological energy transduction; bacterial evolution; sensory processes; biofuels
Research Interests
Biological energy transduction is required for life processes. Our laboratory is actively working on a variety of problems focusing on the mechanism of biological electron transfer. We are particularly interested in the physical and chemical interactions mediating protein-protein interactions which control biological specificity, protein stability and protein dynamics. Our approach to these problems uses a variety of kinetic techniques and structural approaches to relate the time course of events to structural and chemical features of these macromolecules. These techniques include stopped-flow, laser flash photolysis, x-ray crystallography, NMR, site directed mutagenesis, mass spectrometry and as well as computer modeling of the kinetic mechanism and protein structure.
In addition we have a major effort underway to fully characterize and understand the photoactive yellow protein (PYP) from bacteria. This is a sensory protein that is a member of the super family of PAS domain containing signaling proteins, with over 5000 examples found throughout the phylogenetic tree (bacteria to humans). We are using PYP as a model system for the PAS super family, which although having a common structural motif, an incredibly diverse range of stimuli, and an equally diverse array of response regulators. The approaches we utilize parallel those described above, and focus on temporal and structural events leading to the conversion from the resting state to the signaling state and interaction with the response regulator.
Given our focus on bacterial systems, we have active projects of bacterial evolution, bacterial genome sequencing, and utilizing genetic context to identify, unique metabolic pathways.
Finally, we are engaged in developing algae (principally Chlorella and Botryococcus) as a source of hydrocarbons for the production of biofuels in the desert southwest. Our focus here is on using adaptive and genetic engineering to generate strains which produce commercially viable quantities of hydrocarbons, and are optimized for the water quality, carbon dioxide source (flue gas), and temperature ranges available in the southwest.
Selected Publications (last three years)
GHP, a new c-type green heme protein from Halochromatium salexigens and other proteobacteria. Gonzalez Van Driessche, Bart Devreese, John C. Fitch, Terrance E. Meyer, Michael A. Cusanovich, and Jozef J. Van Beeumen, FEBS J. 273, 2801-11 (2006).
Local Stability of Rodobacter capsulatus Cytochrome c2 Probed by Solution Phase Hydrogen/Deuterium Exchange and Mass Spectrometry. Guilong Cheng, Michael A. Cusanovich, Vicki H. Wysocki, J. Am. Soc. Mass Spectrom, 17, 1518-25 (2006).
Photocycle and Photoreversal of Photoactive Yellow Protein at Alkaline pH: Kinetics, Intermediates, and Equilibria. C.P. Joshi, B. Borucki, H. Otto, T.E. Meyer, M.A. Cusanovich, & M.P. Heyn. Biochem. 45, 7057-68 (2006).
The transient accumulation of the signaling state of photoactive yellow protein is controlled by the external pH. Berthold Borucki, Chandra P. Joshi, Harald Otto, Michael A. Cusanovich, and Maarten P. Heyn, Biophysical J., 91, 2991-3001 (2006).
Properties of the Dark and Signaling States of Photoactive Yellow Protein Probed by Solution Phase Hydrogen/Deuterium Exchange and Mass Spectrometry. Guilong Cheng, Michael A. Cusanovich,Vicki H. Wysocki, Biochem. 45, 11744-51 (2006).
Structural role of Y98 in PYP: effects on fluorescence, gateway and photocycle recovery. John A. Kyndt, Savvas N. Savvides, Samy Memmi, Moonjoo Koh, John C. Fitch, Terry E. Meyer, Jozef J. Van Beeumen, and Michael A. Cusanovich, Biochem. 46, 95-105 (2007).
Plasmon Waveguide Resonance (PWR) Spectroscopic Evidence for Differential Binding of Oxidized and Reduced Rhodobacter capsulatus Cytochrome c2 to the Cytochrome bc1 Complex Mediated by the Conformation of the Rieske Iron-Sulfur Protein. S. Devanathan, Z. Salamon, G. Tollin, J.C. Fitch, T.E. Meyer, E.A. Berry, & M.A. Cusanovich, Biochem. 46, 7138-45 (2007).
Role of a conserved salt bridge between the PAS core and the N-terminal domain in the activation of the photoreceptor photoactive yellow protein. Daniel Hoersch, Harald Otto, Chandra P. Joshi, Berthold Borucki, Michael A. Cusanovich and Maarten P. Heyn, Biophysical J. 93, 1687-99 (2007).
The Photoactivated PYP Domain of Rhodospirillum centenum Ppr Accelerates Recovery of the Bacteriophytochrome Domain After White Light Illumination. John A. Kyndt, John C. Fitch, Terry E. Meyer, and Michael A. Cusanovich, Biochem 46, 8256-62 (2007).
Photoactive Yellow Protein from the Halophilic Bacterium Salinibacter ruber. Samy Memmi, John Kyndt, Terry Meyer, Bart Devreese, Michael Cusanovich, and Jozef Van Beeumen, Biochemistry. 47, 2014-24 (2008).
Distinguishing chromophore structures of photocycle intermediates of the photoreceptor PYP by transient fluorescence and energy transfer. Daniel Hoersch, Harald Otto, Michael A. Cusanovich, and Maarten P. Heyn, Journal of Physical Chemistry B 112, 9118-25 (2008).
Occurrence and Evolution of sphaeroides Heme Protein and Diheme Cytochrome c in Purple Photosynthetic Bacteria of the Family Rhohdobacteraceae. Terry Meyer, John Kyndt, and Michael Cusanovich, Photosynthesis Research, in the press (2009).