John P. Richard
B.S., Ohio State University (1974)
Ph.D., Ohio State University (1979)
Postdoctoral Fellow, Brandeis University (1979-82)
Research Associate, Fox Chase Cancer Center (1982-84)
Herchel Smith Fellow in Organic Chemistry, Cambridge University, Cambridge, England (1984-85)
Honors and Awards:
Herchel Smith Fellowship, University of Cambridge, United Kingdom, 1984-1985.
NIH First Award, 1988.
NSF Special Creativity Award, 2007.
2003 T S. Walton Visitor, University College Dublin, Ireland, 2003.
Visiting Professor of Chemistry, Departamento de Química Física, Universidad de Santiago, Spain, August 2003, 2006, 2009 and 2011.
Visiting Professor of Chemistry, Department Chemie, Ludwig-Maximilians-Universität Muenchen, Germany, 2004 and 2010.
Editorial Board of Bioorganic Chemistry, 1998 – present.
Editorial Board of The Journal of Physical Organic Chemistry, 2003 – present.
Editorial Board of Biochemistry, 2010 – present.
Coeditor of Annual Reports on the Progress of Chemistry: Organic Chemistry, 1996-2002.
Editor of Advances in Physical Organic Chemistry, 2000-2012.
Secretary, Division of Biological Chemistry, American Chemical Society, 2003-2008.
Co-Chair Gordon Research Conference on Enzymes, Coenzymes and Metabolic Pathways, 2006.
Chair Gordon Research Conference on Isotopes in Chemistry and Biology, 2010.
Chair of the Organizing Committee for the 22nd Enzyme Mechanisms Conference, 2011.
Organizing Committee, Reaction Mechanisms VII Conference, Dublin, Ireland, 2004.
Advisory Board, IUPAC 19th International Conference on Physical Organic Chemistry, ICPOC-17, 18 and 19, 2006, 2008, 2010.
Jacob Schoellkopf Medal (ACS Western New York Section), 2009.
UB Distinguished Professor of Chemistry, 2012.
Fellow of the American Chemical Society, 2014.
Mechanisms of enzyme-catalyzed reactions and the reactions of small molecules in solution that may be models for enzyme catalysis.
The field of molecular biology requires a community of biologists who possess an intuitive understanding of how to delineate the many complex cellular and higher-order processes which occur in living systems, and of chemists and biochemists who possess the ability to determine the underlying chemical mechanism for these biological processes. Within the latter community studies of enzymes and their reaction mechanisms have long provided a unique understanding of how life functions at a molecular level.
There are many questions that can be raised about the mechanism for uncatalyzed and enzyme-catalyzed reactions of small molecules in water. What are the lifetimes of carbanion and carbenium ion intermediates of these reactions, and how does their lifetime govern the reaction mechanism? Why are some reaction mechanisms stepwise and other mechanisms concerted? What imperatives determine the chemical mechanisms for enzyme-catalyzed reactions? What is the origin of the rate acceleration for enzymatic reactions. What are the intermediates of enzyme-catalyzed reactions, and how are these species stabilized by interaction with the protein catalyst?
Research projects in progress at this time in Professor Richard’s lab include: (1) The determination of the rate and equilibrium constants for addition of nucleophilic reagents to simple carbenium ions and the effect of changing carbenium ion structure on these kinetic and thermodynamic parameters. (2) The generation of biologically important enolates, and development of experimental protocol to estimate the pKas for weak carbon acids. (3) Studies on the mechanism for nonenzymatic and enzyme-catalyzed aldol addition reactions in water. (4) The determination of the mechanistic imperatives for nonenzymatic and enzyme-catalyzed aldose-ketose and allylic isomerization reactions. (5) The characterization of the transition state and intermediates of b-galactosidase catalyzed hydrolysis of glycosides and determination of the function of essential amino-acid residues in the enzymatic reaction.
Selected Recent Publications:
- A. C. Reyes, T. L. Amyes and J. P. Richard, Enzyme Architecture: Self-Assembly of Enzyme and Substrate Pieces of Glycerol-3-Phosphate Dehydrogenase into a Robust Catalyst of Hydride Transfer. J. Am. Chem. Soc., 138, 15251-15259 (2016). 10.1021/jacs.6b09936
- A. C. Reyes, T. L. Amyes and J. P. Richard, “Structure-Reactivity Effects on Intrinsic Primary Kinetic Isotope Effects for Hydride Transfer Catalyzed by Glycerol 3-Phosphate Dehydrogenase”, [Communication] J. Am. Chem. Soc., 138, 14526−14529 (2016). 10.1021/jacs.6b07028
- J. P. Richard, T. L. Amyes, M. Malabanan, X. Zhai, K. Kim, C. J. Reinhardt, R. K. Wierenga, E. J. Drake and A. M. Gulick, “Structure-Function Studies of Hydrophobic Residues that Clamp a Basic Glutamate Side Chain During Catalysis by Triosephosphate Isomerase”, Biochemistry, 55, 3036-3047 (2016). 10.1021/acs.biochem.6b00311.
- A. C. Reyes, T. L. Amyes and J. P. Richard, “Enzyme Architecture: A Startling Role for Asn270 in Glycerol 3-Phosphate Dehydrogenase-Catalyzed Hydride Transfer”, Biochemistry, 55, 1429-1432 (2016). 10.1021/acs.biochem.6b00116.
- X. Zhai, T. L. Amyes and J. P. Richard, “Role of Loop-Clamping Side Chains in Catalysis by Triosephosphate Isomerase”, J. Am. Chem. Soc., 136, 15185-15177 (2015). 10.1021/jacs.5b09328
- B. Goryanova, L. M. Goldman, S. Ming, T. L. Amyes, J. A. Gerlt and J. P. Richard, “Rate and Equilibrium Constants for an Enzyme Conformational Change During Catalysis by Orotidine 5’-Monophosphate Decarboxylase”, Biochemistry, 54, 4555–4564 (2015). 10.1021/acs.biochem.5b00591
- A. C. Reyes, A. P. Koudelka, T. L. Amyes and J. P. Richard, “Enzyme Architecture: Optimization of Transition State Stabilization from a Cation-Phosphodianion Pair”, J. Am. Chem. Soc., [Communication] 136, 5312-5315 (2015). 10.1021/jacs.5b02202
- A. C. Reyes, X. Zhai, K. T. Morgan, C. J. Reinhardt, T. L. Amyes and J. P. Richard, “The Activating Oxydianion Binding Domain for Enzyme-Catalyzed Proton Transfer, Hydride Transfer and Decarboxylation: Specificity and Enzyme Architecture”, J. Am. Chem. Soc., 137, 1372-1382 (2015). [Spotlight Article] 10.1021/ja5123842
- L. M. Goldman, T. L. Amyes, B. Goryanova, J. A. Gerlt and John P. Richard, “Enzyme Architecture: Deconstruction of the Enzyme-Activating Phosphodianion Interactions of Orotidine 5’-Monophosphate Decarboxylase”, J. Am. Chem. Soc., 135, 10156-10165 (2014). 10.1021/ja505037v
- J. P. Richard, T. L. Amyes, B. Goryanova and X. Zhai, “Enzyme Architecture: On the Importance of Being in a Protein Cage”, Curr. Opin. Chem. Biol., 21, 1-10 (2014). 10.1016/j.cbpa.2014.03.001