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.
- Xia, Y. i., Zhou, Y., Carter, D. S., McNeil, M. B., Choi, W., Halladay, J., ... Alley, M. (2018). Discovery of a cofactor-independent inhibitor of Mycobacterium tuberculosis InhA. Life science alliance. 1(3), e201800025-e201800025.
- Lehmann, J., Cheng, T., Aggarwal, A., Park, A. S., Zeiler, E., Raju, R. M., ... Sieber, S. A. (2018). Ein antibakterielles β‐Lacton bekämpft Mycobacterium tuberculosis durch Infiltration der Mykolsäurebiosynthese. Angewandte Chemie. 130(1), 354-359.
- Ganley, J. G., Carr, G., Ioerger, T. R., Sacchettini, J. C., Clardy, J., & Derbyshire, E. R. (2018). Front Cover: Discovery of Antimicrobial Lipodepsipeptides Produced by a Serratia sp. within Mosquito Microbiomes (ChemBioChem 15/2018). Chembiochem : a European journal of chemical biology. 19(15), 1570-1570.
- Negri, A., Javidnia, P., Mu, R., Zhang, X., Vendome, J., Gold, B., ... Somersan-Karakaya, S. (2018). Identification of a Mycothiol-Dependent Nitroreductase from Mycobacterium tuberculosis.. ACS Infectious Diseases. 4(5), 771-787.
- Singh, S. B., Odingo, J., Bailey, M. A., Sunde, B., Korkegian, A., O’Malley, T., ... Parish, T. (2018). Identification of cyclic hexapeptides natural products with inhibitory potency against Mycobacterium tuberculosis. BMC Research Notes. 11(1), 416.
- 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.
- Pai, R., Sacchettini, J. C., & Ioerger, T. R. (2008). Specificity normalization for identifying selective inhibitors in virtual screening. 787-793.
- Yu, M., Kumar, T., Nkrumah, L. J., Sinnis, P., Coppi, A., Valderramos, J., ... Fidock, D. A. (2007). Evidence for the non-essentiality of the Plasmodium candidate drug target enoyl acp reductase. The American Journal of Tropical Medicine and Hygiene. 77(5), 145-145.
- 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. ACS Photonics. 234,
- Romo, T. D., Sacchettini, J. C., Terwilliger, T. C., Adams, P. D., Afonine, P. V., Grosse-Kunstleve, R. W., ... Storoni, L. C. (2007). Automated structure determination with phenix. FUNDAMENTALS OF TRIBOLOGY AND BRIDGING THE GAP BETWEEN THE MACRO-AND MICRO/NANOSCALES. 245, 101-109.
- Gopal, K., Sacchettini, J. C., & Ioerger, T. R. (2007). Database Approaches and Data Representation in Structural Bioinformatics. 425-432.
- 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.
- Wang, Feng (2007-08). Structure-based drug mechanism study and inhibitor design targeting tuberculosis. (Doctoral Dissertation)
- Ramesh, Arati (2007-08). Structural studies of the Ro ribonucleoprotein and the metalloregulator CsoR. (Doctoral Dissertation)
- Yu, Hong (2007-05). Structural studies of Mycobacterium tuberculosis KatG, an INH drug activator, and Brucella abortus VirB11, an ATPase of type IV translocation system. (Doctoral Dissertation)
- Kuo, Mack Ryan (2006-12). Structure, function, and inhibition of enoyl reductases. (Doctoral Dissertation)
- Yang, Dong (2006-08). Structural studies of terpenoid biosynthesis and bacterial cell division. (Doctoral Dissertation)