Keith Munson, PhD

Dr. Munson studies the structure-function relationships of the gastric H,K-ATPase. His short term goals include the design and expression of mutants of the enzyme (both the beta and alpha subunits) and measurement of mutant activity, ion affinity, inhibition constants for the specific inhibitor SCH28080, and membrane targeting. His long term goal is to design specific inhibitors with increased efficacy compared to the currently employed proton pump inhibitors. To approach this goal, he has developed a molecular model of the H,K-ATPase catalytic (alpha) subunit by using computer-assisted homology modeling of the known structure of the srCa-ATPase. Together with the mutational data this has led to identification of the inhibitor binding-site region and to the design of cysteine mutants yielding predicted disulfide linkages supporting the accuracy of the model. The model is also currently serving as a guide to mutation of potential sites of interaction between alpha and beta subunits as well as possible kinase and phosphatase sites identified as a consequence of the modeling.