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.
- Jansen, R. S., Mandyoli, L., Hughes, R., Wakabayashi, S., Pinkham, J. T., Selbach, B., ... Rhee, K. Y. (2020). Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis. Nature Communications. 11(1), 1960.
- Guthrie, L. M., Soma, S., Yuan, S., Silva, A., Zulkifli, M., Snavely, T. C., ... Sacchettini, J. C. (2020). Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice.. Science (New York, N.Y.). 368(6491), 620-625.
- Taira, J., Umei, T., Inoue, K., Kitamura, M., Berenger, F., Sacchettini, J. C., Sakamoto, H., & Aoki, S. (2020). Improvement of the novel inhibitor for Mycobacterium enoyl-acyl carrier protein reductase (InhA): a structure-activity relationship study of KES4 assisted by in silico structure-based drug screening. Journal of Antibiotics. 73(6), 372-381.
- 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.
- Tang, S. u., Hicks, N. D., Cheng, Y., Silva, A., Fortune, S. M., & Sacchettini, J. C. (2019). Structural and functional insight into the Mycobacterium tuberculosis protein PrpR reveals a novel type of transcription factor. Nucleic acids research. 47(18), 9934-9949.
- 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).
- Deaton, J., Savva, C., Sun, J., Sharma, S., Holzenburg, A., Sacchettini, J., & Young, R. (2002). GroEL: A proteinaceous \"Surfactant\"?. MICROSCOPY AND MICROANALYSIS. 8(SUPPL. 2), 840-841.
- Holmes, J. H., Lieberman, J. M., Probert, C. B., Marks, W. H., Hill, M. E., Paull, D. L., ... Hall, R. A. (2001). Elevated intestinal fatty acid binding protein and gastrointestinal complications following cardiopulmonary bypass: a preliminary analysis.. JOURNAL OF SURGICAL RESEARCH. 100(2), 192-196.
- Grimsley, J. K., Disioudi, B. D., Holton, T. R., Sacchettini, J. C., & Wild, J. R. (2000). Active site modifications of organophosphorus hydrolase for improved detoxification of organophosphorus neurotoxins. 33, 223-242.
- Krebs, B., Eicken, C., Gerdemann, C., Buldt-Karentzopoulos, K., Magrini, A., Klabunde, T., & Sacchettini, J. C. (1999). Crystal structure, sequence, and mechanism of catechol oxidase. J Inorg Biochem. 74(1-4), 35-35.
- Ioerger, T. R., Holton, T., Christopher, J. A., & Sacchettini, J. C. (1999). TEXTAL: a pattern recognition system for interpreting electron density maps.. Proc Int Conf Intell Syst Mol Biol. 130-137.
- Reddy, M., Sacchettini, J. C., Zhou, N. E., & Mccutchen, B. F. (2019). Compositions and methods for inhibition of mycobacteria.
- Sacchettini, J. C., Miller, M. W., Wallis, D., Zhou, N. E., & Fossum, T. W. (2019). Compositions and methods for drug sensitization of parasites.
- Sacchettini, J., Zhou, N., Baker, D., Maxwell, S., & Wallis, D. (2018). Compositions and methods for drug-sensitization or inhibition of a cancer cell.
- Rao, J., Cirillo, J., Xie, H., & Sacchettini, J. (2017). ?-lactamase substrates and methods of their use for the diagnosis of tuberculosis.
- 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)