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.
- 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.
- Chen, Q., Shah, K. N., Zhang, F., Salazar, A. J., Shah, P. N., Li, R., ... Cannon, C. L. (2019). Minocycline and Silver Dual-Loaded Polyphosphoester-Based Nanoparticles for Treatment of Resistant Pseudomonas aeruginosa. Molecular Pharmaceutics. 16(4), 1606-1619.
- 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).
- Kieser, K. J., Baranowski, C., Chao, M. C., Long, J. E., Sassetti, C. M., Waldor, M. K., ... Rubin, E. J. (2015). Peptidoglycan synthesis in Mycobacterium tuberculosis is organized into networks with varying drug susceptibility. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES. 112(42), 13087-13092.
- Xie, H., Rao, J., Mire, J., Sacchettini, J. C., Kong, Y., & Cirillo, J. D. (2010). Mtb Bla-specific fluorescent probes for tuberculosis detection and imaging. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY. 240,
- Mosser, R., Reddy, M., Bruning, J., Sacchettini, J. C., & Reinhart, G. D. (2010). Redefining the Role of the Quaternary Shift in the Allosteric Inhibition of Bacillus Stearothermophilus Phosphofructokinase. Biophys J. 98(3), 39A-39A.
- Mosser, R., Reddy, M., Sacchettini, J. C., Igumenova, T., & Reinhart, G. D. (2009). A Solution NMR and Crystallographic Study of the Role of the Quaternary Shift in the Allosteric Regulation of Phosphofructokinase from B. stearothermophilus. Biophys J. 96(3), 5A-5A.
- Pai, R., Sacchettini, J. C., & Ioerger, T. R. (2008). Analysis of protein-ligand interactions using localized stereochemical features. 666-673.
- 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)