个人简介

Professor of Biochemistry, Biophysics and Chemistry. Ph.D. Washington University, St. Louis (1987).

研究领域

Molecular Structure

Professor Sacchettini’s research has primarily focused on the structure-based design and synthesis of novel compounds which are being tested as drug candidates against tuberculosis and malaria. Tuberculosis and malaria are the two most deadly infectious diseases. The Sacchettini lab uses protein crystallography to visualize proteins at their atomic resolution and computer programs to make designer inhibitors. The lab is also applying these techniques to Cancer and Alzheimer’s disease.

近期论文

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Reddy MC, Breda A, Bruning JB, Sherekar M, Valluru S, Thurman C, Ehrenfeld H, Sacchettini JC. "Structure, Activity, and Inhibition of the Carboxyltransferase ß-Subunit of Acetyl Coenzyme A Carboxylase (AccD6) from Mycobacterium tuberculosis." Antimicrob Agents Chemother. 2014 Oct;58(10):6122-32. Nixon MR, Saionz KW, Koo MS, Szymonifka MJ, Jung H, Roberts JP, Nandakumar M, Kumar A, Liao R, Rustad T, Sacchettini JC, Rhee KY, Freundlich JS, Sherman DR. "Folate pathway disruption leads to critical disruption of methionine derivatives in Mycobacterium tuberculosis." Chem Biol. 2014 Jul 17;21(7):819-30. Shi X, Festa RA, Ioerger TR, Butler-Wu S, Sacchettini JC, Darwin KH, Samanovic MI. "The copper-responsive RicR regulon contributes to Mycobacterium tuberculosis virulence" MBio. 2014 Feb 18;5(1). pii: e00876-13. doi: 10.1128/mBio.00876-13. Zhang YJ, Reddy MC, Ioerger TR, Rothchild AC, Dartois V, Schuster BM, Trauner A, Wallis D, Galaviz S, Huttenhower C, Sacchettini JC, Behar SM, Rubin EJ. "Tryptophan biosynthesis protects mycobacteria from CD4 T-cell-mediated killing." Cell. 2013 Dec 5;155(6):1296-308 •Gulten G, Sacchettini JC. "Structure of the Mtb CarD/RNAP ß-lobes complex reveals the molecular basis of interaction and presents a distinct DNA-binding domain for Mtb CarD." Structure. 2013 Oct 8;21(10):1859-69. doi: 10.1016/j.str.2013.08.014. Epub 2013 Sep 19. Small JL, Park SW, Kana BD, Ioerger TR, Sacchettini JC, Ehrt S. "Perturbation of cytochrome c maturation reveals adaptability of the respiratory chain in Mycobacterium tuberculosis." MBio. 2013 Sep 17;4(5):e00475-13. doi: 10.1128/mBio.00475-13. •Lanzas F, Karakousis PC, Sacchettini JC, Ioerger TR. "Multidrug-resistant tuberculosis in Panama is driven by clonal expansion of an MDR-TB strain related to the KZN XDR-TB strain from South Africa." J Clin Microbiol. 2013 Jul 24. Mosser R, Reddy MC, Bruning JB, Sacchettini JC, Reinhart GD. "Redefining the Role of the Quaternary Shift in Bacillus stearothermophilus Phosphofructokinase." Biochemistry. 2013 Jul 16. Stanley SA, Kawate T, Iwase N, Shimizu M, Clatworthy AE, Kazyanskaya E, Sacchettini JC, Ioerger TR, Siddiqi NA, Minami S, Aquadro JA, Schmidt Grant S, Rubin EJ, Hung DT. "Diarylcoumarins inhibit mycolic acid biosynthesis and kill Mycobacterium tuberculosis by targeting FadD32." Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11565-70. Liu Z, Ioerger TR, Wang F, Sacchettini JC. "Structures of Mycobacterium tuberculosis FadD10 Protein Reveal a New Type of Adenylate-forming Enzyme." J Biol Chem. 2013 Jun 21;288(25):18473-83. •Gokulan K, O'Leary SE, Russell WK, Russell DH, Lalgondar M, Begley TP, Ioerger TR, Sacchettini JC. "Crystal structure of Mycobacterium tuberculosis polyketide synthase 11 (PKS11) reveals intermediates in the synthesis of methyl-branched alkylpyrones." J Biol Chem. 2013 Jun 7;288(23):16484-94. •Kinjo T, Koseki Y, Kobayashi M, Yamada A, Morita K, Yamaguchi K, Tsurusawa R, Gulten G, Komatsu H, Sakamoto H, Sacchettini JC, Kitamura M, Aoki S. "Identification of compounds with potential antibacterial activity against Mycobacterium through structure-based drug screening." J Chem Inf Model. 2013 May 24;53(5):1200-12. •Gopinath K, Venclovas C, Ioerger TR, Sacchettini JC, McKinney JD, Mizrahi V, Warner DF. "A vitamin B12 transporter in Mycobacterium tuberculosis." Open Biol. 2013 Feb 13;3(2):120175. •Kim Y, Cunningham MA, Mire J, Tesar C, Sacchettini J, Joachimiak A. "NDM-1, the ultimate promiscuous enzyme: substrate recognition and catalytic mechanism." FASEB J. 2013 Jan 30. •Dejesus MA, Zhang YJ, Sassetti CM, Rubin EJ, Sacchettini JC, Ioerger TR. "Bayesian analysis of gene essentiality based on sequencing of transposon insertion libraries." Bioinformatics. 2013 Mar 15;29(6):695-703. •Anderson JW, Sarantakis D, Terpinski J, Kumar TR, Tsai HC, Kuo M, Ager AL, Jacobs WR Jr, Schiehser GA, Ekins S, Sacchettini JC, Jacobus DP, Fidock DA, Freundlich JS. "Novel diaryl ureas with efficacy in a mouse model of malaria." Bioorg Med Chem Lett. 2013 Feb 15;23(4):1022-5Dejesus MA, Sacchettini JC, Ioerger TR. "Reannotation of translational start sites in the genome of Mycobacterium tuberculosis." Tuberculosis (Edinb). 2013 Jan;93(1):18-25. •Krieger IV, Freundlich JS, Gawandi VB, Roberts JP, Gawandi VB, Sun Q, Owen JL, Fraile MT, Huss SI, Lavandera JL, Ioerger TR, Sacchettini JC. "Structure-guided discovery of phenyl-diketo acids as potent inhibitors of M. tuberculosis malate synthase." Chem Biol. 2012 Dec 21;19(12):1556-67. Zhang YJ, Ioerger TR, Huttenhower C, Long JE, Sassetti CM, Sacchettini JC, Rubin EJ. "Global assessment of genomic regions required for growth in Mycobacterium tuberculosis." PLoS Pathog. 2012 Sep;8(9):e1002946. Epub 2012 Sep 27. Xie H, Mire J, Kong Y, Chang M, Hassounah HA, Thornton CN, Sacchettini JC, Cirillo JD, Rao J. "Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-specific fluorogenic probe." Nat Chem. 2012 Oct;4(10):802-9. Epub 2012 Sep 2. •James JN, Hasan ZU, Ioerger TR, Brown AC, Personne Y, Carroll P, Ikeh M, Tilston-Lunel NL, Palavecino C, Sacchettini JC, Parish T. "Deletion of SenX3-RegX3, a key two component regulatory system of Mycobacterium smegmatis, results in growth defects under phosphate-limiting conditions." Microbiology. 2012 Sep 6. •Chia BS, Lanzas F, Rifat D, Herrera A, Kim EY, Sailer C, Torres-Chavolla E, Narayanaswamy P, Einarsson V, Bravo J, Pascale JM, Ioerger TR, Sacchettini JC, Karakousis PC. "Use of multiplex allele-specific polymerase chain reaction (MAS-PCR) to detect multidrug-resistant tuberculosis in Panama." PLoS One. 2012;7(7):e40456. Epub 2012 Jul 6. Moussa SH, Kuznetsov V, Tran TA, Sacchettini JC, Young R. "Protein determinants of phage T4 lysis inhibition." Protein Sci. 2012 21, 571-582. Mosser R, Reddy MC, Bruning JB, Sacchettini JC, Reinhart GD. "Structure of the apo form of Bacillus stearothermophilus phosphofructokinase." Biochemistry. 2012 51, 769-775. •La Rosa V, Poce G, Canseco JO, Buroni S, Pasca MR, Biava M, Raju RM, Porretta GC, Alfonso S, Battilocchio C, Javid B, Sorrentino F, Ioerger TR, Sacchettini JC, Manetti F, Botta M, De Logu A, Rubin EJ, De Rossi E. "MmpL3 is the cellular target of the antitubercular pyrrole derivative BM212." Antimicrob Agents Chemother. 2012 56, 324-331. •Kim, Y., Tesar, C., Mire, J., Jedrzejczak, R., Binkowski, A., Babnigg, G., Sacchettini, J., and Joachimiak, A. "Structure of apo- and monometalated forms of NDM-1--a highly potent carbapenem-hydrolyzing metallo-beta-lactamase." PLoS One, 2011, 6, e24621. Lotesta, S. D., Liu, J., Yates, E. V., Krieger, I., Sacchettini, J. C., Freundlich, J. S., and Sorensen, E. J. "Expanding the pleuromutilin class of antibiotics by de novo chemical synthesis." Chem Sci 2, 2011, 1258-1261. Madina, B. R., Kuppan, G., Vashisht, A. A., Liang, Y. H., Downey, K. M., Wohlschlegel, J. A., Ji, X., Sze, S. H., Sacchettini, J. C., Read, L. K., and Cruz-Reyes, J. "Guide RNA biogenesis involves a novel RNase III family endoribonuclease in Trypanosoma brucei." RNA 2011. •Gokulan, K., Aggarwal, A., Shipman, L., Besra, G. S., and Sacchettini, J. C. "Mycobacterium tuberculosis acyl carrier protein synthase adopts two different pH-dependent structural conformations." Acta crystallographica 2011 67, 657-669. Vilcheze, C., Baughn, A. D., Tufariello, J., Leung, L. W., Kuo, M., Basler, C. F., Alland, D., Sacchettini, J. C., Freundlich, J. S., and Jacobs, W. R., Jr. "Novel Inhibitors of InhA Efficiently Kill Mycobacterium tuberculosis under Aerobic and Anaerobic Conditions." Antimicrobial agents and chemotherapy 2011 55, 3889-3898. •Ford, C. B., Lin, P. L., Chase, M. R., Shah, R. R., Iartchouk, O., Galagan, J., Mohaideen, N., Ioerger, T. R., Sacchettini, J. C., Lipsitch, M., Flynn, J. L., and Fortune, S. M. "Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection." Nat Genetics 2011 43, 482-486. Picaud, S., Kavanagh, K. L., Yue, W. W., Lee, W. H., Muller-Knapp, S., Gileadi, O., Sacchettini, J., and Oppermann, U. "Structural basis of fumaratehydratase deficiency." J Inherit Metab Dis. 2011 34, 671-676. •Bruning, J. B., Murillo, A. C., Chacon, O., Barletta, R. G., and Sacchettini, J. C. "Structure of the Mycobacterium tuberculosis D-alanine:D-alanine ligase, a target of the antituberculosis drug D-cycloserine." Antimicrobial agents and chemotherapy 2011 55, 291-301. •Dias MV, Snee WC, Bromfield KM, Payne R, Palaninathan SK, Ciulli A, Howard NI, Abell C, Sacchettini JC, Blundell TL. "Structural investigation of inhibitor designs targeting 3-dehydroquinate dehydratase from the shikimate pathway of Mycobacterium tuberculosis." Biochem J. 2011 436, 729-739. •Arockiasamy A, Aggarwal A, Savva CG, Holzenburg A, Sacchettini JC. "Crystal structure of the calcium chelating immunodominant antigen, calcium dodecin (Rv0379), from Mycobacterium tuberculosis with a unique calcium-binding site." Protein Sci. 2011 20, 827-833. •Chim N, Habel JE, Johnston JM, Krieger I, Miallau L, Sankaranarayanan R, Morse RP, Bruning J, Swanson S, Kim H, Kim CY, Li H, Bulloch EM, Payne RJ, Manos-Turvey A, Hung LW, Baker EN, Lott JS, James MN, Terwilliger TC, Eisenberg DS, Sacchettini JC, Goulding CW. "The TB Structural Genomics Consortium: A decade of progress." Tuberculosis (Edinb). 2011 91(2):155-72.