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James Sacchettini

Sacchettini, James
James Sacchettini
Wolfe-Welch Chair in Science, Professor of Biochemistry and Biophysics and of Chemistry
ILSB / Room 2138A
Undergraduate Education
B.A St. Louis University (1980)
Graduate Education
Ph.D. Washington University, St. Louis (1987)
Postdoc. Washington University, St. Louis (1987-89)
Professor. Albert Einstein College of Medicine
Joined Texas A&M in 1996

Crystallography / Drug Design

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.

Recent Publications

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  1. Guthrie, LM, Soma, S, Yuan, S, Silva, A, Zulkifli, M, Snavely, TC et al.. Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice. Science. 2020;368 (6491):620-625.
    doi: 10.1126/science.aaz8899. PubMed PMID:32381719. .

  2. Jansen, RS, Mandyoli, L, Hughes, R, Wakabayashi, S, Pinkham, JT, Selbach, B et al.. Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis. Nat Commun. 2020;11 (1):1960.
    doi: 10.1038/s41467-020-15876-8. PubMed PMID:32327655. PubMed Central PMC7181641.

  3. Taira, J, Umei, T, Inoue, K, Kitamura, M, Berenger, F, Sacchettini, JC et al.. 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. J. Antibiot. 2020;73 (6):372-381.
    doi: 10.1038/s41429-020-0293-6. PubMed PMID:32152525. .

  4. Sun, Q, Li, X, Perez, LM, Shi, W, Zhang, Y, Sacchettini, JC et al.. The molecular basis of pyrazinamide activity on Mycobacterium tuberculosis PanD. Nat Commun. 2020;11 (1):339.
    doi: 10.1038/s41467-019-14238-3. PubMed PMID:31953389. PubMed Central PMC6969166.

  5. Mosior, J, Bourland, R, Soma, S, Nathan, C, Sacchettini, J. Structural insights into phosphopantetheinyl hydrolase PptH from Mycobacterium tuberculosis. Protein Sci. 2020;29 (3):744-757.
    doi: 10.1002/pro.3813. PubMed PMID:31886928. PubMed Central PMC7021004.

  6. Tang, S, Hicks, ND, Cheng, YS, Silva, A, Fortune, SM, Sacchettini, JC et al.. Structural and functional insight into the Mycobacterium tuberculosis protein PrpR reveals a novel type of transcription factor. Nucleic Acids Res. 2019;47 (18):9934-9949.
    doi: 10.1093/nar/gkz724. PubMed PMID:31504787. PubMed Central PMC6765138.

  7. Dragset, MS, Ioerger, TR, Zhang, YJ, Mærk, M, Ginbot, Z, Sacchettini, JC et al.. Genome-wide Phenotypic Profiling Identifies and Categorizes Genes Required for Mycobacterial Low Iron Fitness. Sci Rep. 2019;9 (1):11394.
    doi: 10.1038/s41598-019-47905-y. PubMed PMID:31388080. PubMed Central PMC6684656.

  8. Carey, AF, Rock, JM, Krieger, IV, Chase, MR, Fernandez-Suarez, M, Gagneux, S et al.. Correction: TnSeq of Mycobacterium tuberculosis clinical isolates reveals strain-specific antibiotic liabilities. PLoS Pathog. 2019;15 (6):e1007846.
    doi: 10.1371/journal.ppat.1007846. PubMed PMID:31163081. PubMed Central PMC6548391.

  9. Brown, EE, Miller, AK, Krieger, IV, Otto, RM, Sacchettini, JC, Herman, JK et al.. A DNA-Binding Protein Tunes Septum Placement during Bacillus subtilis Sporulation. J. Bacteriol. 2019;201 (16):.
    doi: 10.1128/JB.00287-19. PubMed PMID:31160399. PubMed Central PMC6657595.

  10. Farhat, MR, Freschi, L, Calderon, R, Ioerger, T, Snyder, M, Meehan, CJ et al.. GWAS for quantitative resistance phenotypes in Mycobacterium tuberculosis reveals resistance genes and regulatory regions. Nat Commun. 2019;10 (1):2128.
    doi: 10.1038/s41467-019-10110-6. PubMed PMID:31086182. PubMed Central PMC6513847.

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