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 electron transfer; biological energy transduction; evolution; sensory processes

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 and perturbation methods as well as computer modeling of the kinetic mechanism and protein structure.

Electron transfer by c-type cytochromes, copper proteins and nonheme iron-sulfur proteins are the focus of our study of biological electron transfer. In general terms we have four principal projects: 

• The use of site-directed mutagenesis to determine the role of specific amino acid side chains in electron transfer and protein stability;
• Studies on naturally occurring complex redox proteins which contain two or more redox clusters, for example, flavocytochrome c from Chromatium vinosum and cytochrome b/c1 from Rhodobacter capsulatus;
• The nature of evolutionary adaptations that have occurred in the redox proteins (periplasmic) of extreme halophiles. Here, the focus is on gram negative bacteria that live in high sodium chloride(up to 25% by weight), and
• We are investigating the properties of the cytochromes c3 (from Desulfovibrio) that allow them to behave as semi-conductors in dried films with the goal of developing new bioelectronic materials.

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 with many features in common with other sensory pigments(for example, rhodopsin in mammalian eyes) and serves as an excellent model system for the biochemistry and biophysics of photoactive proteins. Moreover, PYP has properties which may permit its use as a photoelectric device.

Recent Publications

A sensitive circular dichroism marker for the chromophore environment of Photoactive Yellow Protein: assignment of the 307 and 318 bands to the n6Π* transition of the carbonyl. B. Borucki, H. Otto, T. E. Meyer, M. A. Cusanovich and M. P. Heyn, J. Phys. Chem. B 109, 629-33 (2005).

Photoreversal kinetics of the I₁ and I₂ intermediates in the photocycle of Photoactive Yellow Protein by double flash experiments with variable time-delay. C.P. Joshi, B. Borucki, H. Otto, T. E. Meyer, M. A. Cusanovich and M. P. Heyn, Biochemistry 44, 656-65 (2005).

Thermochromatium tepidum Photoactive Yellow Protein/Bacteriophytochrome/Diguanylate Cyclase: Characterization of the PYP Domain. J. A. Kyndt, J. C. Fitch, T. E. Meyer and M. A. Cusanovich, Biochem. 44, 4755-64 (2005).

Structural evolution of the chromophore in the primary stages of trans/cis isomerization in photoactive yellow protein. K. Heyne, O. F. Mohammed, A. Usman, J. Dreyer, E. T. Nibbering, and M. A. Cusanovich, J. Am. Chem. Soc. 127, 18100-6 (2005).

Time-Resolved Single Tryptophan Fluorescence in Photoactive Yellow Protein Monitors Changes in the Chromophore Structure during the Photocycle via Energy Transfer. H. Otto, D. Hoersch, T. E. Meyer, M. A. Cusanovich, and M. P. Heyn, Biochem. 44, 16804-16 (2005).

Effect of Salt and pH on the Activation of Photoactive Yellow Protein and Gateway Mutants Y98Q and Y98F. B. Borucki, J. A. Kyndt, C. P. Joshi, H. Otto, T. E. Meyer, M. A. Cusanovich, and M. P. Heyn, Biochem. 44, 13650-63 (2005)

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).

Contact Information

Mailing:
Dr. Michael A. Cusanovich, Professor
Department of Biochemistry & Molecular Biophysics
University of Arizona
1041 East Lowell Street
Biosciences West 430
Tucson AZ 85721

Telephone: (520) 621-7533
Fax: (520) 621-6603

Cusanovi@u.arizona.edu

Biological Sciences West
1041 East Lowell Street
P.O. Box 210088 · Tucson, AZ 85721-0088
Tel: (520) 621-5110
FAX (520) 626-9204

Life Sciences South
1007 East Lowell Street
P.O. Box 210106 · Tucson, AZ 85721-0106
FAX (520) 621-3709