My lab uses X-ray crystallography to better understand the relationship between proteins and ligands. Tiny differences in the structure of a molecule can radically change the interaction between a protein and ligand and we are only begining to understand how many factors play a role in this interaction. By manipulating the individual components of a compound it is possible to create a chemical that binds to the protein better than the natural substrate, and prevent the natural reaction from occurring. This is the basis for rational drug design. Our efforts have lead us to collaborations with other labs and scientists in many disciplines as our approach to directed compound design has applications not only in basic research but also in pesticide development, health research and clinical research.
- Sun, Q., Li, X., Perez, L. M., Shi, W., Zhang, Y., & Sacchettini, J. C. (2020). The molecular basis of pyrazinamide activity on Mycobacterium tuberculosis PanD.. Nature Communications. 11(1), 339.
- Brown, E. E., Miller, A. K., Krieger, I. V., Otto, R. M., Sacchettini, J. C., & Herman, J. K. (2019). A DNA-binding protein tunes septum placement during Bacillus subtilis sporulation.. JOURNAL OF BACTERIOLOGY. 201(16),
- Carey, A. F., Rock, J. M., Krieger, I. V., Chase, M. R., Fernandez-Suarez, M., Gagneux, S., ... Fortune, S. M. (2019). Correction: TnSeq of Mycobacterium tuberculosis clinical isolates reveals strain-specific antibiotic liabilities.. PLoS pathogens. 15(6), e1007846-e1007846.
- Farhat, M. R., Freschi, L., Calderon, R., Ioerger, T., Snyder, M., Meehan, C. J., ... Murray, M. (2019). GWAS for quantitative resistance phenotypes in Mycobacterium tuberculosis reveals resistance genes and regulatory regions. Nature Communications. 10(1), 2128.
- Dragset, M. S., Ioerger, T. R., Zhang, Y. J., Maerk, M., Ginbot, Z., Sacchettini, J. C., ... Steigedal, M. (2019). Genome-wide Phenotypic Profiling Identifies and Categorizes Genes Required for Mycobacterial Low Iron Fitness. SCIENTIFIC REPORTS. 9(1), 11394.
- Musa, T. L., Ioerger, T. R., & Sacchettini, J. C. (2009). THE TUBERCULOSIS STRUCTURAL GENOMICS CONSORTIUM: A STRUCTURAL GENOMICS APPROACH TO DRUG DISCOVERY. Advances in protein chemistry and structural biology. STRUCTURAL GENOMICS, PART C. (pp. 41-76).
- Roberts, J. P., Kriger, I., Sun, Q., McKee, E., Ioerger, T. R., Freundlich, J. S., & Sacchettini, J. C. (2007). MEDI 204-Structure-based design, synthesis, and biological evaluation of novel inhibitors of Mycobacterium tuberculosis malate synthase. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. 234,
- Mosser, R., Reddy, M., Sacchettini, J. C., & Reinhart, G. D. (2007). The effect of modifying a fully conserved residue on the allosteric response of bacillus stearothermophilds phosphofructokinase. Biophys J. 42A-42A.
- Schiehser, G. A., Shieh, H., Freundlich, J., Sarantakis, D., Anderson, J., Nevchas, I. K., ... Jacobus, D. P. (2005). 1,3-diaryl ureas and surrogates as inhibitors of Plasmodium falciparum enoyl ACP reductase and potential antimalarial therapeutics. The American Journal of Tropical Medicine and Hygiene. 73(6), 269-270.
- Freundlich, J. S., Anderson, J. W., Sarantakis, D., Shieh, H. M., Lucumi, E., Kuo, M., ... Sacchettini, J. C. (2005). Synthesis, biological activity, and X-ray crystal structural analysis of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase: 2 '- and 4 '-substituted triclosan derivatives. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. 230, U2624-U2625.
- Freundlich, J. S., Shieh, H., Sarantakis, D., Anderson, J., Nevchas, I. K., Terpinski, J., ... Jacobus, D. P. (2005). Synthesis, biological activity, and x-ray crystal structural analysis of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. The American Journal of Tropical Medicine and Hygiene. 73(6), 268-269.
- Sacchettini, J. C., Miller, M. W., Wallis, D., Zhou, N. E., & Fossum, T. W. (2019). Compositions and methods for drug sensitization of parasites.
- Reddy, M., Sacchettini, J. C., Zhou, N. E., & Mccutchen, B. F. (2019). Compositions and methods for inhibition of mycobacteria.
- Rao, J., Cirillo, J. D., Xie, H., & Sacchettini, J. C. (2017). β-lactamase substrates and methods of their use for the diagnosis of tuberculosis.
- Harshbarger, Wayne (2015-05). X-Ray Crystal Structure of Human 20s Proteasome in Complex with Carfilzomib. (Doctoral Dissertation)
- Jung, Hunmin (2014-12). Development of Potent and Selective Inhibitors of Mycobacterium Tuberculosis, Plasmodium Falciparum and Staphylococcus Aureus Dihydrofolate Reductase. (Doctoral Dissertation)
- Joseph, Sonia (2014-08). The Biochemical Investigation and Isolation of Small Molecule Inhibitors for Two Essential Proteins of Mycobacterium tuberculosis H37Rv: IspD and Wag31. (Master's Thesis)
- Lalgondar, Mallikarjun (2014-05). Structural Studies and Evaluation of Inhibitors of Mycobacterium tuberculosis H37Rv Shikimate Dehydrogenase (MtSDH). (Master's Thesis)