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Andrew Karplus
Professor and Department Chair, Biochemistry and Biophysics
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RESEARCH:
Proteins play central roles in all aspects of biochemistry. In addition to the proteins that serve as enzymes catalyzing the reactions of metabolism, there are, among others, structural proteins, protein hormones, transport proteins, cell surface receptors and proteins involved in the regulation of DNA replication and transcription.
A theme common to all classes of proteins is specific recognition and function through unique structure. To develop a better understanding of the mechanisms involved in the specificity of recognition and catalysis, we need detailed structural information. I am interested in using X-ray crystallography, complemented by protein chemistry, enzymology and theoretical approaches such as molecular dynamics, to obtain this detailed structural information. I am also interested in using the structural information for predictive purposes, such as structure-based drug design.
The protein structures we have solved or are working on solving are a diverse group. Proteins are chosen with the dual goal that their detailed study will lead to insights relevant for understanding the particular protein and to insights relevant to understanding general principles of protein structure, stability and function. Current projects include the following: studies of flavoenzymes to investigate how the enzyme:flavin interactions influence the electronic structure of the flavin, and modulate its reactivity (e.g., ferredoxin reductase, old yellow enzyme and trypanothione reductase); studies to investigate the structural and evolutionary relationships among the many cytokines that appear to have a common helical structure (e.g., granulocyte-macrophage colony-stimulating factor and the flt-3 ligand); collaborative studies to obtain structural information in order to guide the engineering of increased catalytic effectiveness of cellulases; and studies of the enzyme urease, which have provided a visualization of catalytically active nickel ions and led to general insight into features of enzyme catalysis.