Date of Award
5-7-2016
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Chemistry
First Advisor
Dr. Aimin Liu
Second Advisor
Dr. Gregory Poon
Third Advisor
Dr. Donald Hamelberg
Abstract
3-Hydroxyanthranilate-3,4-dioxygenase (HAO) is a non-heme iron dependent enzyme that catalyzes the oxidative ring opening of 3-hydroxyanthranilate (HAA) which is an intermediate in the kynurenine pathway and its ring opening is the final enzymatic step from tryptophan to quinolinic acid (QUIN). QUIN functions as an N-methyl-D-aspartate (NMDA) receptor agonist and elevated brain levels of QUIN have been observed in neurodegenerative diseases. Reducing QUIN levels is of pharmacological importance. Kinetic and calorimetric studies were performed on human HAO using UV/Vis spectroscopy and isothermal titration calorimetry to understand its stability and behavior using its natural substrate (3-HAA) and neurological inhibitors such as acetylsalicylic acid (aspirin). This study reveals the first analysis of human HAO and facilitates understanding of its binding dynamics and enzymatic activity which will later support discovering suitable pharmacological compounds.
DOI
https://doi.org/10.57709/8582479
Recommended Citation
Henry, Calmour, "Spectroscopic and Thermodynamic Characterization of Human 3-Hydroxyanthranilate-3,4-Dioxygenase." Thesis, Georgia State University, 2016.
doi: https://doi.org/10.57709/8582479