Theses and Dissertations

ORCID

https://orcid.org/0000-0002-4410-8895

Issuing Body

Mississippi State University

Advisor

Emerson, Joseph P.

Committee Member

Fitzkee, Nicholas C.

Committee Member

Johnsnon, Christopher N.

Committee Member

Stokes, Sean L.

Committee Member

Thornton, Justin A.

Date of Degree

12-13-2024

Original embargo terms

Worldwide

Document Type

Dissertation - Open Access

Major

Chemistry

Degree Name

Doctor of Philosophy (Ph.D.)

College

College of Arts and Sciences

Department

Department of Chemistry

Abstract

ransition metals are micronutrients that play critical roles in all forms of life, acting as stabilizing ions, catalytic centers, and as signaling ions. Due to their importance, classes of biomolecules have been designed with the sole purpose of regulating their intracellular concentrations. One group of which are transcription factors, which regulate intracellular metal concentration by activating or repressing transcription, dependent on metal availability. The activation of transcription factors by metal availability can be attested to conformational changes that are governed by both dynamics and thermodynamics. Due to the influential nature of transcription factors, their activity and activation mode have become a popular research field as well as targets for pharmaceuticals. This dissertation reports the biophysical characterizations of three distinct metal?dependent transcription factors of S. pneumoniae, a facultative anaerobic pathogen, with robust micronutrient regulatory systems. Chapter II describes the Adhesin Competence Repressor (AdcR) is a zinc(II) dependent uptake regulator that, although being biologically and crystallographically characterized, is not well understood in the thermodynamics that govern its activity. Chapter III investigates the Streptococcal czcD activator (SczA), another zinc(II) dependent transcription factor, which controls zinc(II) efflux, and has limited research performed aimed at describing its activity. Chapter IV explores copper regulation by the cop repressor (CopR), an oxidation-dependent transcriptional regulator. Techniques including differential scanning calorimetry (DSC), isothermal titration calorimetry (ITC), circular dichroism (CD), fluorescence spectroscopy, and UV-Vis spectroscopy were utilized to describe the thermodynamics and structural effects of metal ion and DNA binding. These provide insight into the activation mode and regulatory mechanisms of AdcR, SczA, and CopR.

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