Alvan C. Hengge
Department Head and Professor
B.S., 1974, University of Cincinnati
Ph.D., 1987, University of Cincinnati
Postdoctoral, 1987-90, University of Wisconsin
Asst. Scientist, 91-96, Institute for Enzyme Research
Research in my laboratory straddles the fields of biochemistry and organic chemistry. We are interested in characterizing the mechanistic details of chemical reactions, especially those of biological interest. We also study enzymatic catalysis, with the goal of understanding the origins of the tremendous catalytic power of enzymes. Students in my research group learn a wide variety of skills than span the fields of chemistry and biochemistry.
Current projects are examining the chemistry of phosphate esters. These compounds have great importance in biological systems, where their hydrolysis and their formation are catalyzed with remarkable efficiency by enzymes at rates millions of times (or more) faster than analogous uncatalyzed reactions. Our research seeks to understand how enzymes accomplish this remarkable chemistry.
Protein kinases and phosphatases have been called the Yin and Yang of signaling in the cell. In both plants and animals, and from humans to bacteria, protein phosphorylation plays a central role in regulating cellular processes, and in disease. We are studying the mechanisms of catalysis of several of theses enzymes. Some phosphatases utilize a dinuclear metal center in catalysis, while others do not utilize metal ions. Of particular interest is whether these disparate phosphatase families utilize similar, or different, mechanisms to cleave their normally very stable phosphate ester substrates.
A major current focus is on protein-tyrosine phosphatases, a family of enzymes found throughout the biological world. One example is the human PTP-1B, which regulates the receptor for insulin. Another is YopH, a virulence factor in the Yersinia bacteria responsible for bubonic plague. We recently documented an essential role played by protein motions in the catalytic function of both these enzymes, and, quite likely, in the protein-tyrosine phosphatase family as a whole. Our research is funded by the NIH.
Selected Recent Publications
Alvan C. Hengge. “Kinetic Isotope Effects In The Characterization Of Catalysis by Protein Tyrosine Phosphatases.” Biochim. Biophys. Acta.-Proteins and Proteomics 2015, 1854, 1768-1775. DOI: 10.1016/j.bbapap.2015.03.010. PMID: 25840000.
Gwendolyn Moise, Nathan M. Gallup, Anastassia N. Alexandrova, Alvan C. Hengge, and Sean J. Johnson. “Conservative tryptophan mutants of the protein-tyrosine phosphatase YopH exhibit impaired WPD-loop function and crystallize with divanadate esters in their active sites.” Biochemistry, 2015, 54 (42), 6490–6500. DOI: 10.1021/acs.biochem.5b00496. PMID: 26445170.
Sean K. Whittier, Alvan C. Hengge, and J. Patrick Loria. “Conformational Motions Regulate Phosphoryl Transfer in Related Protein Tyrosine Phosphatases.” Science, 2013 (341), 899-903. DOI: 10.1126/science.1241735.
Alvan C. Hengge. “Chemistry and mechanism of phosphatases, diesterases and triesterases.” Biochim. Biophys. Acta. 2013, 1834(1):415-6. DOI: 10.1016/j.bbapap.2012.09.013. PMID: 23267546