Title
Exploration of Sortase A-Inhibitor Binding Mechanisms Through Isothermal Titration Calorimetry
Date of Award
6-13-2017
Document Type
Thesis
Publisher
Santa Clara : Santa Clara University, 2017.
Degree Name
Master of Science (MS)
Department
Bioengineering
First Advisor
Zhiwen Zhang
Abstract
The enzyme Sortase A plays a critical role in the virulence of gram-positive bacteria, facilitating their ability to attach to and infect host tissues. Because of its accessible location on the surface of bacteria and in light of the emergence of antibiotic-resistant bacterial strains, Sortase A has become an important target for novel drugs and their associated research. Here we investigate the thermodynamic characteristics and binding mechanism of Sortase A and inhibitors using isothermal titration calorimetry. The results support a two-step, sequential binding mechanism involving induced fit and conformational change. We recommend that further studies involving other small molecule inhibitors be carried out to evaluate the consistency of the proposed binding mechanisms. Additionally, it may be worthwhile to develop Sortase A inhibitors which mimic peptides given the variable and flexible structure of its active site.
Recommended Citation
Liu, Eddy, "Exploration of Sortase A-Inhibitor Binding Mechanisms Through Isothermal Titration Calorimetry" (2017). Bioengineering Master's Theses. 2.
https://scholarcommons.scu.edu/bioe_mstr/2