John P. Richard

PhD

John Richard

John P. Richard

PhD

John P. Richard

PhD

Research Interests

Mechanism for enzyme-catalyzed reactions: Small molecule model reactions; structure-reactivity studies on mutant enzymes; the role of flexible loops; and, mechanisms for transition-state stabilization

Contact Information

633 Natural Sciences Complex

Buffalo NY, 14260

Phone: (716) 645-4232

Fax: (716) 645-6963

jrichard@buffalo.edu

Education

  • Herchel Smith Fellow in Organic Chemistry, Cambridge University, Cambridge, England, 1984-1985
  • Research Associate, Fox Chase Cancer Center, 1982-1984
  • Postdoctoral Fellow, Brandeis University, 1979-1982
  • PhD, Ohio State University, 1979
  • BS, Ohio State University, 1974

Awards and Honors

  • 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.

Specializations

Mechanisms of enzyme-catalyzed reactions and the reactions of small molecules in solution that may be models for enzyme catalysis.

Research Summary

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

  • Y. S. Kulkarni, Q. Liao, D. Petrović, D. M. Krüger, Birgit Strodel, Tina L. Amyes, John Richard and S. C. L. Kamerlin, "Enzyme Architecture: Modeling the Operation of a Hydrophobic Clamp in Catalysis by Triosephosphate Isomerase", J. Am. Chem. Soc, [Spotlight Article, 10.1021/jacs.7b08573] 139 , 10514-10525  (2017). 10.1021/jacs.7b05576
  • A.  C. Reyes, T.  L. Amyes and J.  P. Richard, “Enzyme Architecture: Erection of Active of Orotidine 5'-Monophosphate Decarboxylase by Substrate-Induced Conformational Changes, [Communication] J. Am. Chem. Soc, 139, 16048-16051 (2017). 10.1021/jacs.7b08897
  • R. He, A. C. Reyes, T. L. Amyes and J. P. Richard, "Enzyme Architecture: The Role of a Flexible Loop in Activation of Glycerol-3-Phosphate Dehydrogenase for Catalysis of Hydride Transfer." Biochemistry, 57, 3227 - 3236 (2018). 10.1021/acs.biochem.7b01282
  • Y. S. Kulkarni, Q. Liao, F. Bylehn, T. L. Amyes, J. P. Richard and S. C. L. Kamerlin The Role of Ligand-Driven Conformational Changes in Enzyme Catalysis: Modeling the Reactivity of the Catalytic Cage of Triosephosphate Isomerase", [Communication], J. Am. Chem. Soc., 139, 3854 -3857 (2018). 10.1021/jacs.8b0025
  • J. P. Richard, T. L. Amyes and A. C. Reyes "Orotidine 5'-Monophosphate Decarboxylase: Probing the Limits of the Possible for Enzyme Catalysis"  Acc. Chem. Res. 51, 960 - 969 (2018). 10.1021/acs.accounts.8b00059
  • X. Zhai, C. J. Reinhardt, M. M. Malabanan, T. L. Amyes,  and J. P. Richard “Enzyme Architecture: Amino Acid Side-chains Which Function to Optimize the Basicity of the Active Site Glutamate of Triosephosphate Isomerase”, J. Am. Chem. Soc., 139, 8277-8286 (2018). 10.1021/jacs.8b04367
  • A.  C. Reyes, T.  L. Amyes and J.  P. Richard, "Primary Deuterium Isotope Effects: A Probe for the Origin of the Rate Acceleration for Hydride Transfer Catalyzed by Glycerol-3-Phosphate Dehydrogenase," Biochemistry 57 4338-4348 (2018). 10.1021/acs.biochem.8b00536
  • A. C. Reyes, D. C. Plache, A. P. Koudelka, T. L. Amyes, J. A. Gerlt, and J. P. Richard, "Enzyme Architecture: Breaking Down the Catalytic Cage that Activates Orotidine 5'-Monophosphate Decarboxylase for Catalysis," J. Am. Chem. Soc. 140, 17580−17590 (2018). 10.1021/jacs.8b09609
  • L. S. Mydy, J. R. Cristobal, R. D. Katigbak, P. Bauer, A. C. Reyes, S. C. L. Kamerlin, J. P. Richard and A. M. Gulick, Human Glycerol 3-Phosphate Dehydrogenase:  X-Ray Crystal Structures that Guide the Interpretation of Mutagenesis Studies. Biochemistry 58, (2019). 10.1021/acs.biochem.8b01103
  • J. P. Richard. "Protein Conformational Flexibility and Stiffness Enables Efficient Enzymatic Catalysis." [Perspective]  J. Am. Chem. Soc. 141  (2019). 10.1021/jacs.8b10836