Distinguished Lecturer: Douglas Rees, Ph.D., Professor of Chemistry, California Institute of Technology, "Nitrogenase: Beyond the Resting State"

Distinguished Bioengineering Lecturer: 

Douglas Rees, Ph.D.

Professor of Chemistry

California Institute of Technology

Faculty Host: Dorit Hanein

Title: Nitrogenase: Beyond the Resting State

Abstract:

The bacterial enzyme nitrogenase has the remarkable ability to catalyze the reduction of dinitrogen to ammonia to under physiological conditions. The mechanistic questions related to how nitrogenase overcomes the kinetic stability of the NN triple bond to fix dinitrogen under ambient conditions have intrigued chemists for the past century. We have applied a structure-based approach to examine how nitrogenase uses iron-sulfur metalloclusters and ATP-dependent electron transfer to reduce dinitrogen and other substrates. A puzzling feature of the nitrogenase mechanism has been how to reconcile the relative stability of the FeMo-cofactor with the reactivity towards dinitrogen. Our studies have established that binding of ligands to nitrogenase under turnover conditions can be accompanied by the distortions and rearrangements of the catalytic FeMo-cofactor; these rearrangements may provide clues how the active site is activated during the catalytic cycle. The complementary strengths of X-ray crystallography and electron microscopy are being used to illuminate the mechanistic foundations of this process.

Bio:

Douglas C. Rees is the Roscoe Gilkey Dickinson Professor of Chemistry at the California Institute of Technology and an Investigator of the Howard Hughes Medical Institute (until August 2025). He received his BS in Molecular Biophysics and Biochemistry from Yale College, working with C.W. Slayman, and his PhD in Biophysics from Harvard University, where he conducted his graduate research in protein crystallography with W.N. Lipscomb. Following a postdoctoral appointment at the University of Minnesota studying nitrogenase with J.B. Howard, Dr. Rees joined the faculty of the Department of Chemistry and Biochemistry at UCLA until moving to Caltech in 1989. The research interests of the Rees group emphasize the general area of structural bioenergetics, using structural and functional approaches to characterize metalloproteins and membrane proteins such as nitrogenase and ABC transporters that mediate ATP-dependent energy transduction processes.