Inhibition of the Proteolytic Activity of Anthrax Lethal Factor by Aminoglycosides

Journal of the American Chemical Society

Volumn 126, Issue 15, 2004, Pages 4774-4775

  Lee, Lac V ^a   Bower, Kristen E ^a   Liang, Fu Sen ^a   Shi, Jin ^a   Wu, Douglass ^a   Sucheck, Steven J ^b   Vogt, Peter K ^a   Wong, Chi Huey ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b Optimer Pharmaceuticals Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENYLATE CYCLASE; AMINOGLYCOSIDE; AMINOGLYCOSIDE ANTIBIOTIC AGENT; ANTHRAX LETHAL FACTOR; BACTERIAL ANTIGEN; BACTERIAL PROTEIN; EDEMA FACTOR; FRAMYCETIN; MITOGEN ACTIVATED PROTEIN KINASE KINASE; PROTECTIVE ANTIGEN; PROTEIN KINASE (CALCIUM,CALMODULIN); PROTEINASE; UNCLASSIFIED DRUG;

ANTHRAX; ARTICLE; BACILLUS ANTHRACIS; BINDING AFFINITY; COMPETITIVE INHIBITION; CRYSTAL STRUCTURE; IN VITRO STUDY; PATHOGENESIS; PROTEIN ASSEMBLY; PROTEIN DEGRADATION; SIGNAL TRANSDUCTION;

ANTIGENS, BACTERIAL; BACILLUS ANTHRACIS; BACTERIAL TOXINS; ENZYME INHIBITORS; FRAMYCETIN; MITOGEN-ACTIVATED PROTEIN KINASES; MODELS, MOLECULAR;

EID: 1842841106     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja0495359     Document Type: Article

References (16)

1. Ascenzi, P.; Visca, P.; Ippolito, G.; Spallarossa, A.; Bolognesi, M.; Montecucco, C. FEBS Lett. 2002, 532, 384-388.
2. Duesbery, N. S.; Webb, C. P.; Leppla, S. H.; Gordon, V. M.; Klimpel, K. R.; Copeland, T. D.; Ahn, N. G.; Oskarsson, M. K.; Fukasawa, K.; Paull, K. D.; Woude, G. F. V. Science 1998, 280, 734-737.
3. Vitale, G.; Bernardi, L.; Napolitani, G.; Mock, M.; Montecucco, C. Biochem. J. 2000, 352, 739-745.
4. Enslen, H.; Davis, R. J. Biol. Cell 2001, 93, 5-14.
5. Maly, D. J.; Choong, C. I.; Ellman, J. A. Proc. Natl. Acad. Sci. U.S.A. 2000 97, 2419-2424.
6. Bunyapaiboonsri, T.; Ramstrom, O.; Lohmann, S.; Lehn, J.-M.; Peng, L.; Goeldner, M. ChemBioChem 2001 2, 438-444.
7. (a) Panchal, R. G.; Hermone, A. R.; Nguyen, T. L.; Wong, T. Y.; Schwarzenbacher, R.; Schmidt, J.; Lane, D.; McGrath, C.; Turk, B. E.; Burnett, J.; Aman, M. J.; Little, S.; Sausville, E. A.; Zaharevitz, D. W.; Cantley, L. C.; Liddington, R. C.; Gussio, R.; Bavari, S. Nat. Struct. Mol. Biol. 2004, 11, 67-72.
8. (b) Tonello, F.; Seveso, M.; Marin, O.; Mock, M.; Montecucco, C. Nature 2002, 418, 386.
9. Turk, B. E.; Wong, T. Y.; Schwarzenbacher, R.; Jarrell, E. T.; Leppla, S. H.; Collier, R. J.; Liddington, R. C.; Cantley, L. C. Nat. Struct. Mol. Biol. 2004, 11, 60-66.
10. Assay condition: 20 mM HEPES pH 7.4, 0.1 mg/mL BSA, 3.3 nM LF, and 1 μM LF-10 quenched fluorescent substrate. Additional Zn(II) was not added as the enzyme has been pre-loaded with Zn from Calbiochem.
11. Approximately 60 synthetic aminoglycosides of tobramycin derivatives and neamine/nebramin dimers, and commercial aminoglycosides (apramycin, butirosin, Geneticin, hygromycin, kanamycin, lividomycin, paromomycin, ribostamycin, sisomicin, spectinomycin, streptinomycin, and tobramycin) were tested during the secondary round of screening.
12. Pannifer, A. D.; Wong, T. Y.; Schwarzenbacher, R.; Renatus, M.; Petosa, C.; Bienkowska, J.; Lacy, D. B.; Collier, R. J.; Park, S.; Leppla, S. H.; Hanna, P.; Liddington, R. C. Nature 2001, 414, 229-233.
13. Morris, G. M.; Goodsell, D. S.; Huey, R.; Olson, A. J. J. Comput. Aided Mol. Des. 1996, 10, 293-304. Aminoglycoside models were built using the Insight II software (Accelrys Inc., San Diego, CA). The AutoDock 3.0.5 (The Scripps Research Institute, San Diego, CA) software package was used for ligand docking experiments. The docking experiments were done with Zn(II) in the active site of LF and confined to a rectangular box surrounding the 40 Å substrate binding cleft.
14. Moazed, D.; Noller, H. F. Nature 1987, 327, 389-394.
15. Agnelli, F.; Sucheck, S. J.; Marby, K. A.; Rabuka, D.; Sears, P. S.; Liang, F.-S.; Wong, C.-H. Angew. Chem. 2004. In press.
16. Tonello, F.; Seveso, M.; Marin, O.; Mock, M.; Montecucco, C. Nature 2002, 418, 386.