Research

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Research

Crystal structure of the N-terminal domain of M. tuberculosis DnaB helicase.
Biswas, T. & Tsodikov, O. V. (2008) FEBS J., 275, 3064-3071.

Research

DNA replication in mycobacteria

Organisms from all kingdoms of life, including viruses, rely on timely and accurate DNA replication to propagate and preserve genetic information from parents to progeny. The genomic revolution in the last decade allowed us to study biological processes in a variety of pathogenic organisms. We study DNA replication mechanisms in pathogenic microorganisms such as Mycobacterium tuberculosis and explore novel approaches to discovery and development of molecules that inhibit these processes. These inhibitory molecules could be used as biochemical probes or further developed into novel anti-infectives.

Theoretical crystallography

Our group is developing analytical tools with the ultimate goal of simplifying determination of macromolecular crystal structures from diffraction data.

Mycobacterium tuberculosis acetyltransferase Eis, responsible for tuberculosis resistance to the drug kanamycin.

Chen, Biswas et al. (2011) Proc. Natl. Acad. Sci. USA, 108, 9804-980.

Oleg Tsodikov laboratory

Department of Pharmaceutical Sciences

University of Kentucky

Mechanisms of Transcriptional Regulation

We are interested in the structure-function relationship of transcription factors, proteins that regulate (or dysregulate) transcription in all domains of life. While normally these transcription factors protect humans from cancer and other diseases, their genetic mutations (as with FLI1 shown in the figure) can reprogram the cell and cause cancer. A combination of structural and biochemical approaches is directed towards understanding transcription factor-driven mechanisms and towards developing agents preventing abnormal transcriptional regulation.

Crystal structure of the DNA binding domain of human transcription factor FLI1 in complex with DNA..

Hou, C. & Tsodikov, O. V. (2015) Biochemistry, 54, 7365-7374.

Drug resistance in tuberculosis

In the course of evolution, Mycobacterium tuberculosis has developed efficient mechanisms of inactivating drugs that would kill most other bacteria. As a consequence, many drug-resistant tuberculosis infections are very difficult to cure, and limited or no therapeutic options can be offered to the patients. In collaboration with Dr. Sylvie Garneau-Tsodikova at the University of Kentucky, we are working on unraveling the elaborate mechanisms of drug resistance of tuberculosis and on developing of novel drugs to treat drug-resistant tuberculosis.