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Mapping Hydrogen Bond Networks in Protein Kinase A

Professor Gianluigi Veglia’s research paper, “Mapping the Hydrogen Bond Networks in the Catalytic Subunit of Protein Kinase A Using H/D Fractionation Factors,” has been selected as an ACS Editor’s Choice. This article was recently published in Biochemistry. In addition Veglia, authors include Geoffrey Li and Jonggul Kim, Department of Chemistry graduate students, Postdoctoral Associate Atul K. Srivastava, Ph.D., and Professor Susan S. Taylor from the University of California, San Diego.

The activity and regulation of the ubiquitous signaling enzyme, protein kinase A, depends on its transition from open to closed state. Detecting the subtle rearrangement of the enzyme is a non-trivial challenge, and requires inventive techniques. In the Biochemistry paper, the Veglia group reports on using equilibrium hydrogen/deuterium exchange (fractionation factors) in conjunction with nuclear magnetic resonance (NMR) as a way to probe the hydrogen bonding network in protein kinase A along the enzymatic pathway. The non-invasive nature of the measurement allowed detecting the intricate allosteric pathways in the enzyme, inaccessible to other methods.

The fractionation factors were first introduced by Maurice Kreevoy, an emeritus of the Chemistry Department, to study low energy barrier hydrogen bonds in di-carboxylic acids. However, this paper shows for the first time that these experiments can be used to trace allostery in enzymes.