Squire J. Booker

Squire J. Booker

Main Content

  • Howard Hughes Medical Investigator
  • Professor of Chemistry
  • Professor of Biochemistry and Molecular Biology
  • Eberly Distinguished Chair in Science
Office:
302 Chemistry Building
University Park, PA 16802
Email:
(814) 865-8793

Mailing Address:
104 Chemistry Bldg.
University Park, PA 16802

Education:

  1. B.A. in chemistry, Austin College, 1987
  2. Ph.D. in biochemistry, Massachusetts Institute of Technology, 1994

Honors and Awards:

  1. 2017 Eberly Distinguished Chair in Science
  2. 2017 Elected to the American Academy of Arts and Sciences
  3. 2017 Lloyd N. Ferguson Distinguished Lecturer at Cal State, Los Angeles
  4. 2016 Penn State Faculty Scholar Medal
  5. 2016 Scott Lectureship in Chemistry and Biochemistry at the University of Florida
  6. 2016 Co-organizer of the ASBMB Annual Meeting
  7. 2015 Selected as Howard Hughes Medical Investigator
  8. 2015 Everson Lectureship in Biochemistry at the University of Wisconsin, Madison
  9. 2013 Elected AAAS (American Association for the Advancement of Science) Fellow
  10. 2013 TY Shen Lectureship in Biological Chemistry at MIT
  11. 2011 American Chemical Society Arthur C. Cope Scholar Award
  12. 2006 Co-Chair, GRC on Enzyme Coenzymes and Metabolic Pathways
  13. 2004 Presidential Early Career Award in Science and Engineering
  14. 2002-2007 NSF Faculty Early Career Award
  15. 1996-1999 NIH Postdoctoral Fellow
  16. 1994-1995 NSF-NATO Postdoctoral Fellow

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.

Information:

 

Research in the Booker Lab focuses on elucidating the chemical mechanisms by which enzymes containing iron-sulfur clusters catalyze chemical reactions. Most ongoing projects deal with members of the Radical S-adenosylmethionine Superfamily, a diverse group of enzymes that employ radical chemistry to catalyze transformations involved in post-transcriptional and post-translational modifications, cofactor biosynthesis, secondary metabolite biosynthesis, and enzyme activation. Radical SAM enzymes share a [4Fe-4S] cluster cofactor that is used to reductively cleave S-adenosylmethionine and form the 5’-deoxyadenosyl radical, a potent oxidant typically used to abstract a hydrogen atom and initiate radical chemistry on the substrate. These remarkable enzymes utilize this initial shared step to catalyze a wide array of transformations including methylations, sulfur insertions, decarboxylations, and complex rearrangements. Using a combination of biochemical, analytical, structural, and spectroscopic techniques, the Booker Lab works to characterize these complex and intriguing reaction mechanisms to provide insight for applications to human health and disease and gain a greater understanding of how Nature has worked to solve difficult chemical problems.

Research Interests:

Biological

Biochemistry; enzymology; protein chemistry

Chemical Biology

Natural Product Biosynthesis and Mechanisms of Radical Dependent Enzymes