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
Email: sjb14@psu.edu
Phone: (814) 865-8793

Research Interests

Mechanisms of cofactor action in enymatic reactions

Graduate Programs

BMMB, CHEM

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

Badding, E. D., Grove, T. L., Gadsby, L. K., LaMattina, J. W., Boal, A. K., Booker, S. J. (2017) Rerouting the pathway for the biosynthesis of the side ring system of nosiheptide: the roles of NosI, NosJ, and NosK. J. Am. Chem. Soc., 139, 5896–5905 (PMID: 28343381).

 

Maiocco, S. J., Arcinas, A. J., Landgraf, B. J., Lee, K. H., Booker S. J., and Elliott, S. J. (2016) Transformation of the FeS clusters of the methylthiotransferases MiaB and RimO, detected by direct electrochemistry. Biochemistry, 55, 5531–5536.

 

Block, E., Booker S. J., Flores-Penalba, S., George, G. N., Gundala, S., Landgraf, B. J., Liu, J., Lodge, S. N., Pushie, M. J., Rozovsky, S., Vattekkatte, A., Yaghi, R., and Zeng, H. (2016) Trifluoroselenomethionine: A new natural amino acid. Chembiochem, 18, 1738–1751.

 

McLaughlin, M. I., Lanz, N. D., Goldman, P. J., Lee, K.-H., Booker, S. J., and Drennan, C. L. (2016) Crystallographic snapshots of sulfur insertion by lipoyl synthase. Proc. Natl. Acad. Sci. USA, 113, 9446–94350.

 

Landgraf, B. J., McCarthy, E. L., and Booker, S. J. (2016) Radical S-adenosylmethionine enzymes in human health and disease. Annu. Rev. Biochem., 85, 485–514 (PMID: 27145839).

 

Esakova, O. A., Silakov, A., Grove, T. L., Saunders, A. H., McLaughlin, M. I., Yennawar, N. H., and Booker, S. J. (2016) Structure of quinolinate synthase from Pyrococcus horikoshii in the presence of its product, quinolinic acid. J. Am. Chem. Soc,, 138, 7224–7227.

 

Schwalm, E. L., Grove, T. L., Booker, S. J., and Boal, A. K. (2016) Crystallographic capture of a radical S-adenosylmethionine enzyme in the act of modifying tRNA. Science, 352, 309–312.

 

Landgraf, B. J. and Booker, S. J. (2016) The stereochemical course of the reaction catalyzed by RimO, a radical SAM methylthiotransferase J. Am. Chem. Soc., 138, 2889–2892.

 

Blaszczyk, A. J., Silakov, A., Zhang, B., Maiocco, S. J., Lanz, N.D., Kelly, W. L., Elliott, S. J., Krebs, C. and Booker, S. J. (2016) Spectroscopic and electrochemical characterization of the iron-sulfur and cobalamin cofactors of TsrM, an unusual radical S-adenosylmethionine methylase. J. Am. Chem. Soc., 138, 3416–3426.

 

Lanz, N. D., Lee, K.-H., Horstmann, A. K., Pandelia, M.-E., Krebs, C., and Booker, S. J. (2016) Characterization of lipoyl synthase from Mycobacterium tuberculosis. Biochemistry, 55, 1372–1383.

 

Lanz, N. D., Rectenwald, J., Wang, B., Kakar, E., Laremore, T., Booker, S. J., and Silakov, A. (2015) Characterization of a radical intermediate in lipoyl cofactor biosynthesis. J. Am. Chem. Soc., 137, 13216­–13219.

 

Rajakovich, L. J., Nørgaard, H., Warui, D. M., Chang, W.-C., Li, N., Booker, S. J., Krebs, C., Bollinger, J. M. Jr., Pandelia, M. E. (2015) Rapid reduction of the differic-peroxyhemiacetal intermediate in aldehyde-deformylating oxygenase by a cyanobacterial ferredoxin: Evidence for a free-radical mechanism. J. Am. Chem. Soc., 137, 11695–11709.

 

Marous, D. R., Lloyd, E. P., Buller, A. R., Mopshos, K. A., Grove, T. L., Blaszczyk, A. J., Booker, S. J., Townsend, C. A. (2015) Consecutive radical S-adenosylmethionine methylations form the ethyl side chain in thienamycin biosynthesis. Proc. Natl. Acad. Sci. USA, 112, 10354–10358.

 

Maiocco, S. J., Grove, T. L., Booker, S. J., and Elliott, S. J. (2015) Electrochemical resolution of the [4Fe–4S] centers of the AdoMet radical enzyme BtrN: evidence of proton-coupling and an unusual, low-potential auxiliary cluster. J. Am. Chem. Soc. 137, 8664–8667.

 

Pandelia, M. E., Lanz, N. D., Booker, S. J., and Krebs, C. (2015) Mössbauer spectroscopy of Fe/S proteins. Biochim. Biophys. Acta, 1853, 1395–1405.

 

Lanz, N. D., and Booker, S. J. (2015) Auxiliary iron-sulfur cofactors in radical SAM enzymes. Biochim. Biophys. Acta, 1853, 1316–1334.

 

Bauerle, M. R., Schwalm, E. L, and Booker, S. J. (2015) Mechanistic diversity of radical SAM-dependent methylation. J. Biol. Chem., 290, 3995–4002.

 

Warui, D. M., Pandelia, M. E., Rajakovich, L. J., Krebs, C., Bollinger, J. M., Jr., and Booker, S. J. (2015) Efficient delivery of long-chain fatty aldehydes from the Nostoc punctiforme acyl–acyl carrier protein reductase to its cognate aldehyde deformylating oxygenase. Biochemistry 54, 1006–10015.

 

Lanz, N. D., Pandelia, M. E., Kakar, E. S., Lee, K.-H., Krebs, C., and Booker, S. J. (2014) Evidence for a catalytically and kinetically competent enzyme-substrate cross-linked intermediate in catalysis by lipoyl synthase. Biochemistry, 53, 4557–4572.

 

Silakov, A., Radle, M. I., Grove, T. L., Bauerle, M. R., Green, M. T., Rosenzweig, A. C., Boal, A. K., and Booker, S. J. (2014) Characterization of a cross-linked protein–nucleic acid substrate radical in the reaction catalyzed by RlmN. J. Am. Chem. Soc., 136, 8221–8228.

 

Goldman, P. J., Grove, T. L., Booker, S. J., and Drennan, C. L. (2013) X-ray analysis of butirosin biosynthetic enzyme BtrN redefines structural motfis for AdoMet radical chemistry. Proc. Natl. Acad. Sci., USA, 110, 15949–15954.

 

Landgraf, B. J., Arcinas, A. J., Lee, K.–H., and Booker, S. J. (2013) Identification of an intermediate methyl carrier in the radical SAM methylthiotransferases, RimO and MiaB. J. Am. Chem. Soc., 135, 15404–15416.

 

Pandelia, M. E., Li, N., Nørgaard, H., Warui, D. M., Rajakovich, L. J. Chang, W.-C., Booker, S. J., Krebs, C., and Bollinger, J. M. (2013) Substrate-triggered addition of dioxygen to the differous cofactor of aldehyde-deformylating oxygenase to form a differic-peroxide intermediate. J. Am. Chem. Soc., 135, 15801–15812.

 

Christensen, Q. H., Grove, T. L., Booker, S. J., Greenberg, E. P. (2013) A high-throughput screen for quorum-sensing inhibitors that target acyl-homoserine lactone synthases. Proc. Natl. Acad. Sci., USA, 110, 13815–13820

 

Landgraf, B. J. and Booker, S. J. (2013) The ylide has landed. Nature, 498, 45–47

 

Goldman, P. J., Grove, T. L., Sites, L. A., McLaughlin, M. I., Booker, S. J., and Drennan, C. L. (2013) X-ray structure of an S-adenosylmethionine radical activase reveals an anaerobic solution for formylglycine posttranslational modification. Proc. Natl. Acad. Sci., USA, 110, 8519–8524

 

Grove, T. L., Ahlum, J. H. Qin, R. M., Lanz, N. D., Radle, M. I., Krebs, C., and Booker, S. J. (2013) Further characterization of Cys-type and Ser-type anaerobic sulfatase maturating enzymes suggests a commonality in mechanism of catalysis. Biochemistry, 52, 2874–2887

 

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.

Honors and Awards

  • 2017 Elected to the American Academy of Arts and Sciences
  • 2017 Lloyd N. Ferguson Distinguished Lecturer at Cal State, Los Angeles
  • 2016 Faculty Scholar Medal
  • 2016 Scott Lectureship in Chemistry and Biochemistry at the University of Florida
  • 2016 Co-organizer of the ASBMB Annual Meeting
  • 2015 Selected as Howard Hughes Medical Investigator
  • 2015 Everson Lectureship in Biochemistry at the University of Wisconsin, Madison
  • 2013 Elected AAAS (American Association for the Advancement of Science) Fellow
  • 2013 TY Shen Lectureship in Biological Chemistry at MIT
  • 2011 American Chemical Society Arthur C. Cope Scholar Award
  • 2006 Co-Chair, GRC on Enzyme Coenzymes and Metabolic Pathways
  • 2004 Presidential Early Career Award in Science and Engineering
  • 2002-2007 NSF Faculty Early Career Award
  • 1996-1999 NIH Postdoctoral Fellow
  • 1994-1995 NSF-NATO Postdoctoral Fellow