Physics Commons^™

Experimental Evidence For A Metallohydrolase Mechanism In Which The Nucleophile Is Not Delivered By A Metal Ion: Epr Spectrokinetic And Structural Studies Of Aminopeptidase From Vibrio Proteolyticus, Amit Kumar, Gopal R. Periyannan, Aaron W. Kittell, Jung Ja Kim, Brian Bennett

Physics Faculty Research and Publications

Metallohydrolases catalyse some of the most important reactions in biology and are targets for numerous chemotherapeutic agents designed to combat bacterial infectivity, antibiotic resistance, HIV infectivity, tumour growth, angiogenesis and immune disorders. Rational design of inhibitors of these enzymes with chemotherapeutic potential relies on detailed knowledge of the catalytic mechanism. The roles of the catalytic transition ions in these enzymes have long been assumed to include the activation and delivery of a nucleophilic hydroxy moiety. In the present study, catalytic intermediates in the hydrolysis of L-leucyl-L-leucyl-L-leucine by Vibrio proteolyticus aminopeptidase were characterized in spectrokinetic and structural studies. Rapid-freeze-quench EPR studies …