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Biochemistry Department - Primary Faculty

Paul R. Carey, Ph.D.

Professor

Education

  • D. Phil.: University of Sussex, England
  • Postdoc: National Research Council of Canada, Ottawa, Canada

Research Interests

Research in the Carey lab focuses on the development and application of Raman spectroscopy to probe the structure and dynamics of enzyme-substrate intermediates. Many studies involve following reactions in single protein and nucleic acid crystals, an approach termed “Raman crystallography”. Thus, compounds such as drug candidates can be infused into crystals and, by employing Raman difference spectroscopy, Raman data are obtained for the drug bound in the active site. Analysis of the data yields structural information that provides key insights into factors such as the molecular basis of drug resistance. A parallel approach on crystals of RNA ribozymes has shown that unique information can be obtained on the properties of active site groups and the chemistry of metal binding. Constant efforts are underway to “push the envelope” to extend the size and complexity of the systems under analysis. Recent experiments provide detailed, time-resolved data on the synthesis of a RNA dimer in a RNAPolymerase-DNA crystalline complex with a molecular weight in excess of 120,000 Daltons.

Selected References

  • Nottingham M., Bethel C. R., Pagadala S. R., Harry E., Pinto A., Lemons Z. A., Drawz S. M., Akker F., Carey P. R., Bonomo R. A., and Buynak J. D.
    “Modifications of the C6-substituent of penicillin sulfones with the goal of improving inhibitor recognition and efficacy”
    Bioorg Med Chem Lett 21 (1): 387-93 (2011).
  • Carey P. R., Chen Y., Gong B., and Kalp M.
    “Kinetic crystallography by Raman microscopy”
    Biochim Biophys Acta : (2010).
  • Chen Y., Eldho N. V., Dayie T. K., and Carey P. R.
    “Probing adenine rings and backbone linkages using base specific isotope-edited Raman spectroscopy: application to group II intron ribozyme domain V”
    Biochemistry 49 (16): 3427-35 (2010). Read article in PubMedCentral
  • Gong B., Chen J. H., Yajima R., Chen Y., Chase E., Chadalavada D. M., Golden B. L., Carey P. R., and Bevilacqua P. C.
    “Raman crystallography of RNA”
    Methods 49 (2): 101-11 (2009). Read article in PubMedCentral
  • Guo M., Spitale R. C., Volpini R., Krucinska J., Cristalli G., Carey P. R., and Wedekind J. E.
    “Direct Raman measurement of an elevated base pKa in the active site of a small ribozyme in a precatalytic conformation”
    J Am Chem Soc 131 (36): 12908-9 (2009). Read article in PubMedCentral
  • Kalp M., Bethel C. R., Bonomo R. A., and Carey P. R.
    “Why the extended-spectrum beta-lactamases SHV-2 and SHV-5 are "hypersusceptible" to mechanism-based inhibitors”
    Biochemistry 48 (41): 9912-20 (2009). Read article in PubMedCentral
  • Kalp, M., Totir, M. A., Buynak, J. D. and Carey, P. R.
    “Different Intermediate Populations Formed by Tazobactam, Sulbactam, and Clavulanate Reacting with SHV-1 β-lactamase: Raman Crystallographic Evidence.”
    J Amer. Chem. Soc. 131, 2338-47, (2009).
  • Kalp, M., and Carey, P. R.
    “Carbapenems and SHV-1 β-lactamase Form Different Acyl-Enzyme Populations in Crystals and Solution”
    Biochemistry 47, 11830-37, (2008).
  • Gong, B., Chen, Y. Y., Christian, E. L., Chen, J. H., Chase, E., Chadalavada, D. M., Yajima, R., Golden, B. L., Bevilacqua, P. C., and Carey, P. R.
    “Detection of Inner-sphere Interactions between Magnesium Hydrate and the Phosphate Backbone of the HDV Ribozyme Using Raman Crystallography”
    J. Am. Chem. Soc. 130: 9670-72, (2008).
  • Helfand M. S., Taracila M. A., Totir M. A., Bonomo R. A., Buynak J. D., van den Akker F., and Carey P. R.
    “Raman crystallographic studies of the intermediates formed by Ser130Gly SHV, a beta-lactamase that confers resistance to clinical inhibitors”
    Biochemistry 46 (29): 8689-99 (2007).
  • Gong, B., Chen, J.H., Chase, E., Chadalavada D.M., Yajima R., Golden B.L., Bevilacqua P.C., and Carey, P. R.
    “Direct measurement of pKa near neutrality for the catalytic cytosine in genomic HDV ribozyme using Raman crystallography”
    J. Amer. Chem. Soc. 129: 13335-13342, (2007).
  • Carey, P. R.
    “Raman Crystallography and Other Biochemical Applications of Raman Microscopy”
    Ann. Rev. Phys. Chem. 57: 527-554, (2006).
  • Hall P. R., Zheng R., Antony L., Pusztai-Carey M., Carey P. R., and Yee V. C.
    “Transcarboxylase 5S structures: assembly and catalytic mechanism of a multienzyme complex subunit”
    EMBO J 23 (18): 3621-31 (2004). Read article in PubMedCentral
  • Hall P. R., Zheng R., Pusztai-Carey M., van den Akker F., Carey P. R., and Yee V. C.
    “Expression and crystallization of several forms of the Propionibacterium shermanii transcarboxylase 5S subunit”
    Acta Crystallogr D Biol Crystallogr 60 (Pt 3): 521-3 (2004).

Raman Microscopy

Raman Microscope

 

Paul Carey Faculty's publications at pubmed more in the biochembook