Biochemistry and Molecular Biology
Penn State Science
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Squire Booker

Squire Booker

Main Content

  • Howard Hughes Medical Investigator
  • Professor of Chemistry and
  • Professor of Biochemistry and Molecular Biology
302 Chemistry Building
University Park, PA 16802
Phone: (814) 865-8793

Research Interests

Mechanisms of cofactor action in enymatic reactions

Graduate Programs


Research Summary

Mechanisms of Cofactor Action in Enzymatic Reactions

Enzymes carry out biochemical reactions with astronomical rate enhancements and amazing stereoselectivities, mediating the huge quantity and variety of cellular transformations that constitute what is vaguely termed “life.” Our laboratory is endeavoring to understand at the detailed molecular level the reaction mechanisms employed by various enzymes, and then to exploit what we learn to impact favorably on human health and the human condition in general. A particular focus is to understand the manner in which enzymes bind and use cofactors—whether simple metal ions, complex metal clusters, or small molecules—to increase their catalytic capabilities beyond that which is supported by the functional groups of the twenty naturally occurring amino acids. To characterize enzymes and interrogate their modes of action, we use traditional biochemical and enzymological approaches in combination with structural methods such as X-ray crystallography and various forms of spectroscopy, as well as small-scale organic synthesis and fast-reaction kinetic methods. A growing interest in our lab has been to understand the mechanisms of enzymes that catalyze posttranslational modification of proteins by catalysis that proceeds through organic radical intermediates.   Particular focus is on enzymes that use iron-sulfur clusters and/or S-adenosylmethionine in catalysis.

enzymes that use iron-sulfur clusters and/or S-adenosylmethionine in catalysis

Selected Publications

  • Matthews, M. L., Neumann, C. S., Miles, L. A., Grove, T. L., Booker, S. J., Krebs, C., Walsh, C. T., Bollinger, J. M. Jr. (2009) Substrate positioning controls the partition between halogenation and hydroxylation in the aliphatic halogenase, SyrB2. Proc. Natl. Acad. Sci. USA 106, 17723–17728.
  • Saleh, L., Lee, K.-H., Anton, B. P., Madinger, C. L., Benner, J. S. Roberts, R. J. Krebs, C. and Booker, S. J. (2009) Characterization of RimO, a new member of the methylthioltransferase subclass of the radical SAM superfamily. Biochemistry 48, 10162–10174.
  • Booker, S. J. (2009) Anaerobic functionalization of unactivated C–H bonds (2009). Curr. Opin. Chem. Biol. 13, 58–73.
  • Chatterjee, A., Li, S., Zhang, Y., Grove, T. L., Lee, M., Krebs, C., Booker, S. J., Begley, T. P., Ealick, S. E. (2008) Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily. Nat. Chem. Biol. 4, 758-765.
  • Saunders, A. H., Griffiths, A. E., Lee, K.-H., Cicchillo, R. M., Tu, L. Stromberg, J. A., Krebs, C., and Booker, S. J. (2008) Characterication of quinolinate synthases from Escherichia coli, Mycobacterium tuberculosis, and Pyrococcus horikoshii indicates that [4Fe-4S] clusters are common cofactors throughout this class of enzymes. Biochemistry 47, 10999-1012.