Case Western Reserve University

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 of a spectroscopic technique to define the molecular details of biochemical reactions. In particular, Raman spectroscopy is used to probe the structure and dynamics of enzyme-substrate complexes. A recent development has been to carry out these studies in single protein 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 oh 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 data provide detailed, time-resolved data on the reaction pathway within a RNAase-DNA complex with a molecular weight in excess of 120,000 Daltons.

Selected References

• 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).
• 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).

Raman Microscopy