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.
- Klabunde, T., Petrassi, H. M., Oza, V. B., Raman, P., Kelly, J. W., & Sacchettini, J. C. (2000). Erratum: Rational design of potent human transthyretin amyloid disease inhibitors (Nature Structural Biology (2000) 7 (312-321)). NATURE STRUCTURAL BIOLOGY. 7(5), 431.
- Klabunde, T., Petrassi, H. M., Oza, V. B., Raman, P., Kelly, J. W., & Sacchettini, J. C. (2000). Rational design of potent human transthyretin amyloid disease inhibitors (vol 7, pg 312, 2000). NATURE STRUCTURAL BIOLOGY. 7(5), 431-431.
- Lücke, C., Zhang, F., Hamilton, J. A., Sacchettini, J. C., & Rüterjans, H. (2000). Solution structure of ileal lipid binding protein in complex with glycocholate. The FEBS Journal. 267(10), 2929-2938.
- Klabunde, T., Petrassi, H. M., Oza, V. B., Raman, P., Kelly, J. W., & Sacchettini, J. C. (2000). Rational design of potent human transthyretin amyloid disease inhibitors. Nature Structural and Molecular Biology. 7(4), 312-321.
- Petrassi, H. M., Klabunde, T., Sacchettini, J., & Kelly, J. W. (2000). Structure-Based Design of N -Phenyl Phenoxazine Transthyretin Amyloid Fibril Inhibitors. Journal of the American Chemical Society. 122(10), 2178-2192.
- 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).
- Lücke, C., Fushman, D., Ludwig, C., Hamilton, J. A., Sacchettini, J. C., & Rüterjans, H. (1999). A comparative study of the backbone dynamics of two closely related lipid binding proteins: Bovine heart fatty acid binding protein and porcine ileal lipid binding protein. Lipid Binding Proteins within Molecular and Cellular Biochemistry. (pp. 109-121). Springer Us.
- Scapin, G., Young, A., Kromminga, A., Veerkamp, J. H., Gordon, J. I., & Sacchettini, J. C. (1993). High resolution X-ray studies of mammalian intestinal and muscle fatty acid-binding proteins provide an opportunity for defining the chemical nature of fatty acid: protein interactions. Cellular Fatty Acid-Binding Proteins II. (pp. 3-13). Springer Us.
- Cistola, D. P., Sacchettini, J. C., & Gordon, J. I. (1990). 13C NMR studies of fatty acid-protein interactions: comparison of homologous fatty acid-binding proteins produced in the intestinal epithelium. Cellular Fatty Acid-binding Proteins. (pp. 101-110). Springer Us.
- Sacchettini, J. C., Banaszak, L. J., & Gordon, J. I. (1990). Expression of rat intestinal fatty acid binding protein in E. coli and its subsequent structural analysis: a model system for studying the molecular details of fatty acid-protein interaction. Cellular Fatty Acid-binding Proteins. (pp. 81-93). Springer Us.
- SACCHETTINI, J. C., GORDON, J. I., VANCAMP, S. L., & SCAPIN, G. (1991). THE TERTIARY STRUCTURES OF FATTY-ACID BINDING-PROTEINS. ACS Photonics. 202, 15-BIOL.
- SACCHETTINI, J. C., GORDON, J. I., & BANASZAK, L. J. (1988). PROTEIN LONG CHAIN FATTY-ACID INTERACTIONS - A X-RAY CRYSTALLOGRAPHIC STUDY USING E-COLI-DERIVED RAT INTESTINAL FATTY-ACID BINDING-PROTEIN. The FASEB Journal. 2(5), A1044-A1044.
- SACCHETTINI, J. C., SAID, B., SCHULZ, H., HEUCKEROTH, R. O., & GORDON, J. I. (1986). THE AMINO-ACID-SEQUENCE OF RAT-HEART FATTY-ACID BINDING-PROTEIN. Fed Proc. 45(6), 1635-1635.
- 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)