Department of Chemistry

Xavier University of Louisiana

Neil R. McIntyre, Ph.D.
Ph.D. (Chemistry) University of South Florida, 2008
B.Sc. (Joint Advanced Major in Chemistry and Biology) St. Francis Xavier University, 2001

Assistant Professor of Chemistry

Telephone Number: 504-520-5083
Room Number: NCF - Room 301K
Email Address:


Biochemistry Lecture (CHM 3130)
Biochemistry Laboratory (CHM 3130L)
Enzymology Lecture (CHM 4160)

Short Professional Biography

Dr. McIntyre graduated in 2001 with a Joint Advanced Major in Chemistry and Biology from St. Francis Xavier University (Antigonish, Nova Scotia). Here, his undergraduate research project focused on the synthesis and characterization of nitrogen donor adducts and polymers of trans-bis(oxalato) ruthenium(III). In graduate school, Dr. McIntyre'Äôs research concentrated on the catalysis of several metallo-oxygenases including tyrosinase, dopamine b-monooxygenase (DbM), and peptidylglycine a-amidating monooxygenase (PAM).¬† Under the direction of Dr. David Merkler, the doctoral dissertation focused primarily on steady-state kinetics, kinetic isotope effects and computational studies of PAM. Post-doctoral research was completed at the University of South Florida, College of Medicine, Department of Biochemistry and Molecular Biology (later renamed Molecular Medicine) supervised by Dr. Gloria Ferreira. Dr. McIntyre'Äôs post-doctoral fellowship studied the terminal enzyme in heme biosynthesis. Specifically, the kinetic and resonance Raman spectroscopic characterization of ferrochelatase variants was undertaken to better understand the relationship between metal ion selectivity and porphyrin orientation. In fall 2009, Dr. McIntyre left the University of South Florida to accept an assistant professorship in the Xavier University Chemistry Department.

Research Interest

Within nature'Äôs toolbox, enzymes are biological catalysts critical to metabolic regulation. ¬†The hallmark features of enzymes are their enormous rate-enhancement (typically 106-14 fold increase), selectivity and specificity for reactions they catalyze in their active sites.¬† Like all catalysts, enzymes have the highest binding affinity for transition states along their reaction coordinates.¬† The increased transition state binding affinity arises from the intramolecularity of the enzyme-substrate complex and can actually alter the reaction pathway versus an uncatalyzed reaction, resulting in a different transition state.¬† My group studies the protein chemistry of enzymes with primary expertise is with the type-2 copper enzyme peptidylglycine alpha-hydroxylating monooxygenase (PHM).¬†

PHM is the oxidoreductase domain of the bi-functional enzyme PAM (peptidylglycine alpha-amidating monooxygenase). Peptidylglycine a-amidating monooxygenase (PAM) plays an important role in higher vertebrates catalyzing the amidation of C-terminal glycine-extended peptide hormones.  Amidation is a highly conserved post-translational modification occurring in over half of all known bio-peptides. These post-translationally modified amidated hormones are the foundation of a conserved ancient vertebrate endocrine system based on PAM catalysis.  High levels of PAM are found within the neurosecretory vesicles, as well as many neuronal and endocrine cells with high abundance in the pituitary gland.  The PAM reaction is primarily utilized in vivo for the bio-activation of peptide hormones through catalytic cleavage of an a-C-N bond, truncating the glycine-ultimate substrate to its corresponding amide. PAM is the only known enzyme to catalyze peptide amidation. Dysregulated peptide amidation, either overexpression or impairment, is problematic due to the diverse physiological function of these molecules.  Associated with cancer, amidated peptides are widely known to serve as autocrine or paracrine growth factors in several tumor types and contribute to malignancy.

In addition to the important physiological role, the mechanism within the PHM domain of PAM is catalytically unique and worthy of in-depth study.  The reaction mechanism utilizes a copper-superoxo radical as a nucleophile which cleaves an aliphatic a-C-H bond, forming a copper-hydroperoxo complex which is reduced following an intermolecular electron transfer (through water) from a second copper domain 11 Å away!  The reduction is followed by the formation of an inner-sphere alcohol which is subsequently hydrolyzed, yielding the S-hydroxy product.  The a-C-H bond is characterized by quantum mechanical hydrogen tunneling.  The hallmark features of quantum mechanical (QM) hydrogen tunneling in peptidylglycine a-hydroxylating monooxygenase (PHM) is the temperature-independent intrinsic kinetic isotope effects above the semi-classical limit (~10) while primary kinetic isotope effects displayed temperature dependence allowing deduction of a non-adiabatic full tunneling model.  

Current research in the McIntyre Group:

  • Study the role of PAM in a number of cancers towards novel methodologies for early detection and therapeutic design.
  • Utilize kinetic isotope effects to further characterize the quantum mechanical hydrogen tunneling reaction coordinate of PHM.
  • Design and characterization of biomimetic complexes based on the Cu domain(s) of PHM.¬†¬†
Using a multi-tiered approach, the mechanism of this important and enigmatic catalyst will be examined using a balance of kinetic, chemical, modeling and theoretical approaches. Specifically, techniques such as steady-state and transient state kinetics, coupled with kinetic isotope effects, structure-function analysis, enzyme mutagenesis and computational simulation will reveal novel targeting regimes based on the geometry of reaction intermediates and contribute information essential to the development of chemical catalysts based on PHM reactivity.

Current Grant Support

Louisiana Cancer Research Consortium (LCRC) Bridge Grant
Howard Hughes Medical Institute Scicomp

Recent Publications

Chew GH, Galloway LC, McIntyre NR, Schroder LA, Richards KM, Miller SA, Wright DW, Merkler DJ. Ubiquitin and ubiquitin-derived peptides as substrates for peptidylglycine alpha-amidating monooxygenase. FEBS Lett. 2005; 579(21): 4678-84.

McIntyre NR, Lowe EW Jr, Chew GH, Owen TC, Merkler DJ. Thiorphan, tiopronin, and related analogs as substrates and inhibitors of peptidylglycine alpha-amidating monooxygenase (PAM). FEBS Lett. 2006; 580(2):521-32.

Weiss, SJ, McIntyre, NR, McLaughlin, ML, Merkler, DJ. The development of molecular clamps as drugs. Drug Discov. Today 2006; 11(17-18):819-24.

Merkler, DJ, Asser, AS, Baumgart, LE, Carballo, N, Carpenter, SE, Chew, GH, Cosner, CC, Dusi, J, Galloway, LC, Lowe, AB, Lowe, EW Jr., King III, L, Kendig, RD, Kline, PC, Malka, R, Merkler, KA, McIntyre, NR, Romero, M, Wilcox, BJ and Owen, TC. Substituted Hippurates and Hippurate Analogs as Substrates and Inhibitors of Peptidylglycine a-Hydroxylating Monooxygenase (PHM). Bioorg Med Chem. 2008; 16(23):10061-74.

McIntyre, N.R., Lowe, E.W. Jr., and Merkler, D.J. Imino-Oxy Acetic Acid Dealkylation as Evidence for an Inner-Sphere Alcohol Intermediate in the Reaction Catalyzed by Peptidylglycine a-Hydroxylating Monooxygenase (PHM).  Journal of the American Chemical Society, 2009, 131(29):10308-19.

\McIntyre, N.R., Lowe, E.W.Jr., Belof, J.L., Ivkovic, M., Shafer, J., Space, B. and Merkler, D.J. Evidence for Substrate Pre-organization in the Peptidylglycine a-Amidating Monooxygenase (PAM) Reaction Describing the Contribution of Ground State Structure to Hydrogen Tunneling.   Journal of the American Chemical Society, 2010, 132(46):16393-402.

McIntyre, N.R., Franco, R., Shelnutt, J.A., and Ferreira, G.C.  Porphyrin Interactions with Nickel(II) Chelatase Variants Directly Evolved from Murine Ferrochelatase.  Biochemistry 2011,50(9):1535-44.

Johanson K.E., Watt T.J., McIntyre N.R., Thompson M.  Purification and characterization of enzymes from yeast: An extended undergraduate laboratory sequence for large classes. Biochemical and Molecular Biology Education, 2013, 41(4):251-61.

Lowe, E.W.Jr., McIntyre, N.R., Battistini,M.R., and Merkler, D.J. Inactivation of Peptidylglycine a-Hydroxylating Monooxygenase by Cinnamic Acid Analogs. Archives of Biochemistry and Biophysics. Accepted.

Department of Chemistry