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

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.
  • SUNY Distinguished Professor of Chemistry, 2019
  • NIH MIRA Award, 2020.

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.

Research Publications

Selected Research Publications

  • M. S. Pereira, S. S. de Araújo, R. A. P. Nagem, J.  P. Richard, and T. A. S. Brandão, "The Role of Remote Flavin Adenine Dinucleotide Pieces in the Oxidative Decarboxylation Catalyzed by Salicylate Hydroxylase", Bioorganic Chemistry, 119, 105561 (2022). doi.10.1016/j.bioorg.2021.105561
  • J. R. Cristobal and J. P. Richard, "Glycerol-3-Phosphate Dehydrogenase: The K120 and K204 Side Chains Define an Oxyanion Hole at the Enzyme Active Site", Biochemistry, 61, 856-867 (2022). doi/10.1021/acs.biochem.2c00053
  • P. L. Fernandez and J. P. Richard, "Adenylate Kinase-Catalyzed Reactions of AMP in Pieces: Specificity for Catalysis at the Nucleoside Activator and Dianion Catalytic Sites",  Biochemistry, 61, 2766-2775 (2022). doi/10.1021/acs.biochem.2c00531               
  • J. P. Richard, “The Enabling Role of Ligand-Driven Conformational Changes in Enzyme Evolution”, Perspective Article in Biochemistry, 61, 1533-1542 (2022). 0.1021/acs.biochem.2c00178
  • J. R. Cristobal and J. P. Richard, "Kinetics and Mechanism for Enzyme-Catalyzed Reactions of Substrate Pieces", Methods in Enzymology, Vol. 685, J. P. Richard and G. Moran (Eds.), Academic Press, Cambridge (USA) 95-126 (2023). org/10.1016/bs.mie.2023.03.002
  • J. P. Richard, "The Role of the Substrate Phosphodianion in Catalysis by Orotidine 5'-Monophosphate Decarboxylase," Viewpoint Article in Biochemistry, 62, 969-970 (2023). 10.1021/acs.biochem.3c00031
  • R. Hegazy,  G. Cordara, R. K. Wierenga, and J. P. Richard, "The Role of Asn11 in Catalysis by Triosephosphate Isomerase", Biochemistry, 62 1794-1806 (2023). doi.10.1021/acs.biochem.3c00133
  • J. R. Cristobal, R. N. Nagorski and J. P. Richard,  "Utilization of Cofactor Binding Energy for Enzyme Catalysis: Formate Dehydrogenase-Catalyzed Reactions of the Whole NAD Cofactor and Cofactor Pieces",  Biochemistry, 62, 2314-2324 (2023). doi.org/10.1021/acs.biochem.3c00290
  • R. Hegazy and J. P. Richard, "Triosephosphate Isomerase: The Crippling Effect of the P168A/I172A Substitution at the Heart of an Enzyme Active Site", Biochemistry, 62, 2916-2927 (2023). doi.org/10.1021/acs.biochem.3c00414
  • P. E. Yeary and J. P. Richard, "Changes in Mechanism and Transition State Structure for Solvolysis Reactions of Ring Substituted Benzyl Chloride in Aqueous Solution", J. Phys. Org. Chem., doi.org/10.1002/poc.4600
  • J. R. Cristobal, R. Hegazy,  and J. P. Richard, "Glycerol 3-Phosphate Dehydrogenase: Role of the Protein Conformational Change in Activation of a Readily Reversible Enzyme-Catalyzed Hydride Transfer Reaction", Biochemistry, 63, 1016-1025 (2024). doi.org/10.1021/acs.biochem.3c00702