Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Wells, James A.
Location University of California, San Francisco
Primary Field Biochemistry
Secondary Field Biophysics and Computational Biology
 Election Citation
Wells has revolutionized the science of protein engineering, developing techniques that have enabled the rational design of enzymes, hormones, protein cell-surface receptors, and drugs. In his own laboratory, his new techniques have illuminated many properties of the enzyme subtilisin and of human growth hormone.
 Research Interests
My research is focused on molecular recognition in proteins and on new technologies for analysis and design of proteins and small molecules for biomedical and industrial applications. With others, I have studied key elements in catalysis and specificity in the bacterial serine protease, subtilisin, using mutational methods. Subtilisin is very adaptable enzyme and virtually every functional property has been engineered, including substrate turn-over, specificity, stability, and oxidative resistance. Our group also studies protein-protein recognition. We discovered that binding of human growth hormone (hGH) dimerizes and activates its receptor. We are also interested in the energetics of protein-protein interfaces and on designing molecular mimics for them. Although these contact interfaces cover a large surface area, we found that only a compact group of residues near the center of the interface, termed "hot spots," are crucial for binding. Such hot spots suggest it may be possible to generate small molecules that will bind at these interfaces and facilitate drug discovery.

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