X-RAY CRYSTALLOGRAPHY

Structural biology leverages the three-dimensional shape assumed by macromolecules like proteins and nucleic acids to understand the function and evolutionary history of the molecule.   We use X-ray crystallography to determine the atomic resolution structures of Mtb proteins, alone and in complex with other proteins, natural ligands, and inhibitors.  Practical applications of this endeavor include the manipulation and inhibition of protein function by the rational design of small molecule ligands.  The resulting functional modulators can be used to probe the physiological roles of proteins in the intact cell, and can serve as leads for the development of new therapeutics.  Multiple structures and small molecule inhibitors developed by the TBSGC are driving current TB drug discovery efforts. 

(A) – protein crystals in crystallization drop;  (B) – crystal mounted on X-ray instrument for data collection; (C) – protein crystal diffraction pattern image; (D) – electron density map of a high resolution diffracting protein crystal; (E) – crystal structure of inhibitor TAM16 bound to its target protein (PMID: 28669536), with the omit Fo-Fc electron density map displayed for the inhibitor, and key contacts to the protein highlighted.

We use wide array of crystallization techniques and collect X-ray diffraction data on home source instruments as well as at major US synchrotrons.