Dr. Paul Fitzpatrick's lab studies the regulatory and catalytic properties of the aromatic amino acid hydroxylases tyrosine hydroxylase (TyrH) and phenylalanine hydroxylase (PheH). TyrH, the key enzyme in the biosynthesis of the catecholamine neurotransmitters, utilizes a non-heme iron atom to catalyze oxygen activation and addition. The enzyme is regulated by phosphorylation and feedback inhibition.
PheH, an allosteric enzyme deficient in phenylketonuria, has a similar catalytic mechanism and a similar structure, but differs in its regulatory properties. We utilize a range of biochemical and biophysical techniques, from single turnover kinetics to NMR spectroscopy.
Meisburger, Steve P., Taylor, Alexander B., Khan, Crystal A., Zhang, Shengnan, Fitzpatrick, Paul F., and Ando, Nozomi (2016) “Domain movements upon activation of phenylalanine hydroxylase characterized by crystallography and chromatography-coupled small-angle X-ray scattering” J. Amer. Chem. Soc. 138, 6506-6516 PMC4896396
Zhang, Shengnan, Huang, Tao, Ilangovan, Udayar, Hinck, Andrew P., and Fitzpatrick, Paul F. (2014) “The Solution Structure of the Regulatory Domain of Tyrosine Hydroxylase” J. Mol. Biol. 426, 1483-1497
Zhang, Shengnan, and Fitzpatrick, Paul F. (2016) “Identification of the Allosteric Site for Phenylalanine in Rat Phenylalanine Hydroxylase” J. Biol. Chem. 291, 7418-7425
Fitzpatrick, Paul F. (2015) “Structural Insight into the Regulation of Aromatic Amino Acid Hydroxylation” Curr. Opinion Struct. Biol. 35, 1-6