||Paul F. Fitzpatrick
Office Phone: (210) 567-8264
Office: 5.206.4 Allied Health Building, UT Health Science Center San Antonio
Areas of Specialization
• Bioorganic Chemistry
• Bioinorganic Chemistry
Dr. Fitzpatrick studies the mechanisms and structures of redox-active enzymes:
Flavin-dependent amine and alcohol oxidases. The mechanism of oxidation of amines, amino acids, alcohols and hydroxy acids are being studied to determine the mechanisms of carbon-hydrogen bond cleavage during oxidation of the carbon-heteroatom bond. Rapid-reaction kinetics and kinetic isotope effects for wild-type and mutant enzymes are used to determine the structures of transition states and the roles of the protein structure in catalysis.
Tetrahydropterin-dependent aromatic amino acid hydroxylases. Phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase are mononuclear non-heme iron enzymes that utilize an Fe(IV)O intermediate to hydroxylate their substrates. A variety of spectroscopic and kinetic approaches are being used to characterize intermediates in their reactions and the roles of the protein structure in controlling their reactivities.
"Reduction and Oxidation of the Active Site Iron in Tyrosine Hydroxylase: Kinetics and Specificity"
Frantom, Patrick A., Seravalli, Javier, Ragsdale, Stephen W., and Fitzpatrick, Paul F.
(2006) Biochemistry 45, 2372-2379
"Mechanistic Studies of the Flavoenzyme Tryptophan 2-Monooxygenase: Deuterium and 15N Kinetic Isotope Effects on Alanine Oxidation by an L-Amino Acid Oxidase"
Ralph, Erik C., Anderson, Mark A., Cleland, W. Wallace, and Fitzpatrick, Paul F.
(2006) Biochemistry 45, 15844-15852
"Insights into the Mechanism of Flavoprotein-Catalyzed Amine Oxidation from Nitrogen Isotope Effects on the Reaction of N-Methyltryptophan Oxidase"
Ralph, Erik C., Hirschi, Jennifer S., Anderson, Mark A., Cleland, W. Wallace, Singleton, Daniel A., and Fitzpatrick, Paul F.
(2007) Biochemistry 46, 7655-7664.
"Direct Spectroscopic Evidence for a High-Spin Fe(IV) Intermediate in Tyrosine Hydroxylase"
Eser, Bekir E., Barr, Eric W., Frantom, Patrick A., Saleh, Lana, Bollinger, J. Martin, Jr., Krebs, Carsten, and Fitzpatrick, Paul F.
(2007) J. Amer. Chem. Soc. 129, 11334-11335
"Kinetic Isotope Effects on Aromatic and Benzylic Hydroxylation by Chromobacterium Violaceum Phenylalanine Hydroxylase as Probes of the Chemical Mechanism and Reactivity"
Panay, Aram J., and Fitzpatrick, Paul F.
Biochemistry 47, 11118-11124
"pH Dependence of a Mammalian Polyamine Oxidase: Insights into Substrate Specificity and the Role of Lysine 315"
Henderson Pozzi, Michelle, Gawandi, Vijay, and Fitzpatrick, Paul F.
Biochemistry 48, 1508-1516
"Spectroscopy and Kinetics of Wild-Type and Mutant Tyrosine Hydroxylase: Mechanistic Insight into O2 Activation"
Chow, Marina S., Eser, Bekir E., Wilson, Samuel A., Hedman, Britt, Hodgson, Keith O., Fitzpatrick, Paul F., and Solomon Edward I.
(2009) J. Amer. Chem. Soc. 131, 7685-7698
"Demonstration of a Peroxide Shunt in the Tetrahydropterin-Dependent Aromatic Amino Acid Monooxygenases"
Pavon, Jorge Alex, and Fitzpatrick, Paul F.
(2009) J. Amer. Chem. Soc. 131, 4582-4583
"Identification by Hydrogen/Deuterium Exchange of Structural Changes in Tyrosine Hydroxylase Associated with Regulation"
Wang, Shanzhi, Sura, Giri R., Dangott, Lawrence J., and Fitzpatrick, Paul F.
Biochemistry 48, 4972-4979
"Use of pH and Kinetic Isotope Effects to Establish Chemistry As Rate-Limiting in Oxidation of a Peptide Substrate by LSD1"
Gaweska, Helena, Henderson Pozzi, Michelle, Schmidt, Dawn M. Z., McCafferty, Dewey G., and Fitzpatrick, Paul F.
Biochemistry 48, 5440-5445