Frey


Email

4404D Biochemical Sciences Building
440 Henry Mall
Madison, WI 53706-1544
USA


Office: (608) 262-0055
Secretary: (608) 262-3362
Fax: (608) 262-2904

   

Perry A Frey

           

Emeritus Professor 2008-present
Professor 1981-2007
Robert H. Abeles Professor of Biochemistry,
B.S., Ohio State University;
Ph.D., Brandeis University

      

Mechanisms of enzyme and coenzyme action; stereochemistry and mechanisms of phospho- and nucleotidyl transferase action; structure and function of multienzyme complexes

The central thrust of my research is the elucidation of the mechanisms of enzymatic reactions. Two aspects of the field of mechanistic enzymology are particularly interesting to me, and are the basis for ninety percent of my research:

a) The question of how enzymes utilize binding interactions directed to nonreacting parts of substrate molecules to catalyze the chemical transformations of the reacting parts of substrates is one principal focus of my research. These interactions provide the energy for the structural transition of enzymes into active conformations. Statements that are commonly advanced to explain enzymatic catalysis by the active conformation of an enzyme include those in which the enzyme is postulated to stabilize transition states or to destabilize ground states in enzyme-substrate complexes, or both. These are very general statements that do not explicitly account for the actions of particular enzymes. A specific description of catalysis, in both structural and dynamic terms, is needed for a few enzymes. Serine proteases, isomerases, and the enzymes of galactose metabolism are subjects of my research in this field; and,

b) The second focus of my research is the elucidation of the mechanisms of enzymatic reactions that are so obscure in chemical terms that no obvious chemical precedent is available. These enzymes depend upon cofactors about which little is known. Lysine 2,3-aminomutase is one example of such an enzyme, and it is one subject of my current research in this field. Lysine 2,3-aminomutase catalyzes the 1,2-amino group migration in the interconversion of L-lysine and L-beta-lysine. The required cofactors include pyridoxal-5'-phosphate (PLP), S-adenosylmethionine, and an iron-sulfur cluster. PLP normally functions to stabilize carbanions in enzymatic reactions; however, in the lysine 2,3-aminomutase reaction it appears to facilitate the rearrangement of a substrate radical. S-Adenosylmethionine is normally a biological alkylating agent; however, in the lysine 2,3-aminomutase reaction it functions as a hydrogen transfer agent. Analogous vitamin B12-dependent aminomutases are also under investigation. The chemical interactions of these cofactors and the mechanisms by which they function in catalysis are under investigation. The detailed structure of the enzyme and the chemistry by which it interacts with cofactors are also under intensive investigation by use of physical, chemical and biological methods.



    

 

 

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