Mechanistic studies on a bimetallic aminopeptidase

Brandeis University, Waltham MA

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Abstract

DESCRIPTION (provided by applicant): The research that Dr. Brandt proposes to conduct at Brandeis University for his postdoctoral training shall be a structural enzymology investigation of the catalytic activity of the enzyme aminopeptidase (AAP). AAP is the prototype of a class of physiologically and clinically important enzymes, proteins ranging from DNA polymerase to methane monooxygenase. All of these enzymes share a common catalytic feature: two metal ions connected by a bridging ligand. The crystal structure of AAP has been determined, and dozens of other bridged bimetalloenzymes have also had their structures solved, but how the two metal ions cooperate in catalysis is still unknown. Dr. Brandt has proposed a series of crystallographic and biochemical studies to address this important question. Although the project builds on certain aspects of his graduate work, it represents a significant extension, because it includes learning not only protein crystallography, but also time-resolved crystallography. The project thus represents an ideal mix of front-line research and training.