Biochemistry & Biophysics

James C. Sacchettini

sacchettini Professor of Biochemistry and Biophysics and of Chemistry; Wolfe-Welch Chair in Science
Director, Center for Structural Biology
Chemistry/Biology Interface Training Program
Molecular Biophysics Training Program
Program in Microbial Genetics and Genomics

Phone: (979) 862-7636
Email: sacchett@tamu.edu
Visit the Sacchettini Lab Home Page
B.A St. Louis University (1980)
Ph.D. Washington University, St. Louis (1987)
Postdoc. Washington University, St. Louis (1987-89)

Joined Texas A&M faculty 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
  1. Ioerger TR, Koo S, No EG, Chen X, Larsen MH, Jacobs WR Jr, Pillay M, Sturm AW & Sacchettini JC (2009) Genome analysis of multi- and extensively-drug-resistant tuberculosis from KwaZulu-Natal, South Africa. PLoS One 4: e7778
  2. Sun Q, Kuty GF, Arockiasamy A, Xu M, Young R & Sacchettini JC (2009) Regulation of a muralytic enzyme by dynamic membrane topology. Nat Struct Mol Biol 16: 1192-4
  3. Reddy MC, Palaninathan SK, Bruning JB, Thurman C, Smith D & Sacchettini JC (2009) Structural insights into the mechanism of the allosteric transitions of the mycobacterium tuberculosis cAMP receptor protein. J Biol Chem
  4. Palaninathan SK, Mohamedmohaideen NN, Orlandini E, Ortore G, Nencetti S, Lapucci A, Rossello A, Freundlich JS & Sacchettini JC (2009) Novel transthyretin amyloid fibril formation inhibitors: synthesis, biological evaluation, and X-ray structural analysis. PLoS One 4: e6290
  5. Swanson S, Gokulan K & Sacchettini JC (2009) KasA, another brick in the mycobacterial cell wall. Structure 17: 914-5
  6. Payne K, Sun Q, Sacchettini J & Hatfull GF (2009) Mycobacteriophage Lysin B is a novel mycolylarabinogalactan esterase. Mol Microbiol 73: 367-81
  7. Ioerger TR & Sacchettini JC (2009) Structural genomics approach to drug discovery for Mycobacterium tuberculosis. Curr Opin Microbiol 12: 318-25
  8. Barkan D, Liu Z, Sacchettini JC & Glickman MS (2009) Mycolic acid cyclopropanation is essential for viability, drug resistance, and cell wall integrity of Mycobacterium tuberculosis. Chem Biol 16: 499-509
  9. Freundlich JS, Wang F, Vilchèze C, Gulten G, Langley R, Schiehser GA, Jacobus DP, Jacobs WR Jr & Sacchettini JC (2009) Triclosan derivatives: towards potent inhibitors of drug-sensitive and drug-resistant Mycobacterium tuberculosis. ChemMedChem 4: 241-8
  10. Yu M, Kumar TR, Nkrumah LJ, Coppi A, Retzlaff S, Li CD, Kelly BJ, Moura PA, Lakshmanan V, Freundlich JS, Valderramos JC, Vilcheze C, Siedner M, Tsai JH, Falkard B, Sidhu AB, Purcell LA, Gratraud P, Kremer L, Waters AP, Schiehser G, Jacobus DP, Janse CJ, Ager A, Jacobs WR Jr, Sacchettini JC, Heussler V, Sinnis P & Fidock DA (2008) The fatty acid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites. Cell Host Microbe 4: 567-78
  11. Reddy MC, Kuppan G, Shetty ND, Owen JL, Ioerger TR & Sacchettini JC (2008) Crystal structures of Mycobacterium tuberculosis S-adenosyl-L-homocysteine hydrolase in ternary complex with substrate and inhibitors. Protein Sci 17: 2134-44
  12. Cho Y, Ioerger TR & Sacchettini JC (2008) Discovery of novel nitrobenzothiazole inhibitors for Mycobacterium tuberculosis ATP phosphoribosyl transferase (HisG) through virtual screening. J Med Chem 51: 5984-92
  13. Palaninathan SK, Mohamedmohaideen NN, Snee WC, Kelly JW & Sacchettini JC (2008) Structural insight into pH-induced conformational changes within the native human transthyretin tetramer. J Mol Biol 382: 1157-67
  14. Vilchèze C, Av-Gay Y, Attarian R, Liu Z, Hazbón MH, Colangeli R, Chen B, Liu W, Alland D, Sacchettini JC & Jacobs WR Jr (2008) Mycothiol biosynthesis is essential for ethionamide susceptibility in Mycobacterium tuberculosis. Mol Microbiol 69: 1316-29
  15. Dey S, Burton RL, Grant GA & Sacchettini JC (2008) Structural analysis of substrate and effector binding in Mycobacterium tuberculosis D-3-phosphoglycerate dehydrogenase. Biochemistry 47: 8271-82
  16. Javid-Majd F, Yang D, Ioerger TR & Sacchettini JC (2008) The 1.25 A resolution structure of phosphoribosyl-ATP pyrophosphohydrolase from Mycobacterium tuberculosis. Acta Crystallogr D Biol Crystallogr 64: 627-35
  17. Zwart PH, Afonine PV, Grosse-Kunstleve RW, Hung LW, Ioerger TR, McCoy AJ, McKee E, Moriarty NW, Read RJ, Sacchettini JC, Sauter NK, Storoni LC, Terwilliger TC & Adams PD (2008) Automated structure solution with the PHENIX suite. Methods Mol Biol 426: 419-35
  18. Mohamedmohaideen NN, Palaninathan SK, Morin PM, Williams BJ, Braunstein M, Tichy SE, Locker J, Russell DH, Jacobs WR Jr & Sacchettini JC (2008) Structure and function of the virulence-associated high-temperature requirement A of Mycobacterium tuberculosis. Biochemistry 47: 6092-102
  19. Chinnaswamy S, Yarbrough I, Palaninathan S, Kumar CT, Vijayaraghavan V, Demeler B, Lemon SM, Sacchettini JC & Kao CC (2008) A locking mechanism regulates RNA synthesis and host protein interaction by the hepatitis C virus polymerase. J Biol Chem 283: 20535-46
  20. Alahari A, Trivelli X, Guérardel Y, Dover LG, Besra GS, Sacchettini JC, Reynolds RC, Coxon GD & Kremer L (2007) Thiacetazone, an antitubercular drug that inhibits cyclopropanation of cell wall mycolic acids in mycobacteria. PLoS One 2: e1343
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