![Denis L. Rousseau](https://assets.montefioreeinstein.org/profiles/images/52-denis-rousseau.jpg)
Denis L. Rousseau, Ph.D.
- Professor, Department of Biochemistry
Area of research
- Cytochrome c oxidase structure, function and dynamics. Catalytic mechanism of the membrane-bound enzymes probed by time resolved resonance Raman scattering, time resolved X-ray crystallography and cryogenic electron microscopy.
Phone
Location
- Albert Einstein College of Medicine Jack and Pearl Resnick Campus 1300 Morris Park Avenue Ullmann Building 325 Bronx, NY 10461
Research Profiles
Professional Interests
In our laboratory the mechanisms and properties of cytochrome c oxidase is being investigated. Cytochrome c oxidase, a 400 kDa membrane-bound protein, is the terminal enzyme in the electron transfer chain. Physiologically, it reduces oxygen to water and utilizes the redox energy to translocate protons across the mitochondrial membrane. The enzyme is responsible for over 90% of the oxygen consumption by living organisms in the biosphere; yet the mechanism of its basic function, the coupling between the redox processes and proton translocation is undetermined. Our objective is to obtain a quantitative description of the manner by which oxygen is reduced to water by exploiting laser spectroscopic methods and rapid mixing techniques developed in our laboratory. These studies will allow us to identify the ligand structures in the reaction site of the intermediates in the catalytic reaction.
We are also using two advanced technologies, Serial Femtosecond X-ray Crystallography (SFX) and cryogenic Electron Microscopy (cryo-EM) to determine the structure of the protein matrix in cytochrome c oxidase. With SFX we use a free electron X-ray laser at the Linac Coherent Light Source (LCLS) at SLAC to determine the entire structure of the catalytic intermediates by time-resolved X-ray scattering. In the cryo-EM studies we embed the cytochrome c oxidase in a nanodisc and use the microscopes at the New York Structural Biology Center to determine the structure of the single particles to evaluate the chemical intermediates and the interaction of the enzyme with substrates and small molecule metabolites.
This integrated approach is allowing us to make important advances in establishing the molecular basis for one of the most important enzymes in bioenergetics.
Selected Publications
Structural insights into functional properties of the oxidized form of cytochrome c oxidase
I. Ishigami, R.G. Sierra, S. Zhen, A. Peck, C. Wang, F. Poitevin, S. Lisova, B. Hayes, F. R. Moss III, S. Boutet, R. E. Sublett, C. H. Yoon, S.-R. Yeh & D. L. Rousseau
Nature Comm. Accepted (2023).
Detection of a geminate photoproduct of bovine cytochrome c oxidase by time-resolved serial femtosecond crystallography
I. Ishigami, S. Carbajo, N. Zatsepin, J. Coe, M. Hikita, M. H. Seaberg, R. G. Sierra, M. S. Hunter, P. Fromme, R. Fromme, G. Nelson, T. Grant, S. Basu, C. Conrad, D. L. Rousseau & S.-R. Yeh
J. Am. Chem. Soc. Accepted (2023).
Temperature-dependent structural transition following X-ray-induced metal center reduction in oxidized cytochrome c oxidase
I. Ishigami, S. Russi, A. Cohen, S.-R. Yeh & D. L. Rousseau
J. Biol. Chem. 298, 101799 (2022).
Snapshot of an oxygen intermediate in the catalytic reaction of cytochrome c oxidase
I. Ishigami, A. Lewis-Ballester, A. Echelmeier, G. Brehm, N.A. Zatsepin, T.D. Grant, J.D. Coe, S. Lisova, G. Nelson, S. Zhang, Z.F. Dobson, S. Boutet, R.G. Sierra, A. Batyuk, P. Fromme, R. Fromme, J.C.H. Spence, A. Ros, S.R. Yeh & D.L. Rousseau.
Proc Natl Acad Sci (U S A). 116, 3572-3577. (2019).
Crystal structure of CO-bound cytochrome c oxidase determined by serial femtosecond X-ray crystallography at room temperature
I. Ishigami, N.A. Zatsepin, M. Hikita, C.E. Conrad, G. Nelson, J.D. Coe, S. Basu, T.D. Grant, M.H. Seaberg, R.G. Sierra, M.S. Hunter, P. Fromme, R. Fromme, S.R. Yeh & D.L. Rousseau.
Proc Natl Acad Sci (U S A). 114, 8011-8016 (2017).
Proton translocation in cytochrome c oxidase: Insights from proton exchange kinetics and vibrational spectroscopy.
I. Ishigami, M. Hikita, T. Egawa, S.-R. Yeh & D. L. Rousseau
Biochim Biophys Acta. 1847, 98-108 (2015)
Time-Dependence of the Catalytic Intermediates in Cytochrome c Oxidase.
S. Han, S. Takahashi & D. L. Rousseau
J. Biol. Chem. 275, 1910-1919 (2000).