Presentation Type
Oral/Paper Presentation
Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading global health challenge, particularly due to its ability to enter a dormant, drug-tolerant state that enables long-term persistence within the host. Just before dormancy, Mtb replicates its entire genome creating DNA precursors for when the infection reactivates. Ribonucleotide reductases (RNRs) play a critical role in bacterial survival by catalyzing the conversion of ribonucleotides into deoxyribonucleotides, a necessary step for DNA replication and repair. The class II RNR, NrdZ, has been implicated in facilitating Mtb persistence under hypoxic stress conditions, yet its structural and mechanistic function remains largely uncharacterized. This project aims to elucidate the structural basis of NrdZ function and its role in Mtb dormancy. Through protein purification, crystallization, and X-ray diffraction or cryogenic electron microscopic analysis, we seek to determine the three-dimensional structure of NrdZ and identify key active site residues critical for its enzymatic activity. By structurally defining the molecular mechanisms underlying NrdZ function, this study will provide crucial insights into bacterial adaptation and survival strategies, potentially informing novel therapeutic approaches against persistent TB infections.
Faculty Mentor
Jamaine Davis PhD
Recommended Citation
Jacob, Leah, "Structural basis of a class II ribonucleotide reductase found if Mycobacterium tuberculosis" (2025). Student Scholar Symposium. 37.
https://digitalcollections.lipscomb.edu/student_scholars_symposium/2025/Full_schedule/37
Included in
Biochemistry Commons, Biophysics Commons, Molecular Biology Commons, Structural Biology Commons
Structural basis of a class II ribonucleotide reductase found if Mycobacterium tuberculosis
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading global health challenge, particularly due to its ability to enter a dormant, drug-tolerant state that enables long-term persistence within the host. Just before dormancy, Mtb replicates its entire genome creating DNA precursors for when the infection reactivates. Ribonucleotide reductases (RNRs) play a critical role in bacterial survival by catalyzing the conversion of ribonucleotides into deoxyribonucleotides, a necessary step for DNA replication and repair. The class II RNR, NrdZ, has been implicated in facilitating Mtb persistence under hypoxic stress conditions, yet its structural and mechanistic function remains largely uncharacterized. This project aims to elucidate the structural basis of NrdZ function and its role in Mtb dormancy. Through protein purification, crystallization, and X-ray diffraction or cryogenic electron microscopic analysis, we seek to determine the three-dimensional structure of NrdZ and identify key active site residues critical for its enzymatic activity. By structurally defining the molecular mechanisms underlying NrdZ function, this study will provide crucial insights into bacterial adaptation and survival strategies, potentially informing novel therapeutic approaches against persistent TB infections.