Douglas C. Rees

Board Member: 1999 - 2002

Current Institution
California Institute of Technology
Division of Chemistry & Chemical Engineering

Scholar: 1984

Awarded Institution
University of California, Los Angeles


Research Interests

Enzyme Structure and Catalytic Function

Research in the Rees group focuses on structure-function relationships in macromolecules, using X-ray diffraction methods as the primary experimental approach. The crystallographic structures provide a foundation for understanding the relationships between enzyme structure and catalytic function (particularly in electron transfer systems), for describing the fundamental energetic interactions that determine and stabilize macromolecular structures (especially for membrane proteins, and for proteins isolated from hyperthermophilic bacteria), and for illuminating the structural basis of molecular recognition and binding specificity. Macromolecular systems presently under crystallographic analyses include:

Nitrogenase. The biological conversion of dinitrogen to ammonia is catalyzed by the nitrogenase enzyme system, which consists of two component proteins, the iron (Fe-) protein and the molybdenum-iron (MoFe-) protein. We have determined the three-dimensional structures of both proteins and associated metal centers, which are being used to develop mechanistic models for the nitrogenase reaction.

Extremely Thermostable Metalloproteins. The structures of the tungsten containing aldehyde ferredoxin oxidoreductase and a rubredoxin from Pyrococcus furiosus, an archaeon that grows optimally at 100_C, have been determined. The structures are under study to help identify the origins of the extreme thermostability of these proteins.

A model for the complex of the two component proteins of the nitrogenase system that catalyzes the reduction of atmospheric dinitrogen to ammonia during the process of biological nitrogen fixation.

Membrane Proteins. Structural and sequence analyses of membrane proteins indicate that the same general structural and energetic considerations appear to govern the three-dimensional structures of both water-soluble and membrane proteins. Currently, crystallographic studies of the integral membrane proteins succinate quinone oxidoreductase and photosynthetic reaction centers are underway to both assess the generality of this conclusion and to establish the structural organization of the redox centers.

Fibroblast Growth Factors. FGFs stimulate the growth and development of many different cell types. We have solved the structures of two members of the FGF family, and have recently determined how the anti-ulcer drug sucrose octasulfate and heparin fragments bind to FGF. Collaborative studies are also underway to probe the structures of nucleic acid complexes, transcriptional regulators and a variety of other electron transfer proteins.