Botulinum neurotoxin a protease: Discovery of natural product exosite inhibitors

Journal of the American Chemical Society

Volumn 132, Issue 9, 2010, Pages 2868-2869

  Šilhár, Peter ^a   Čapková, Kateřina ^a   Salzameda, Nicholas T ^a   Barbieri, Joseph T ^b   Hixon And, Mark S ^c   Janda, Kim D ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b MEDICAL COLLEGE OF WISCONSIN   (United States)

^c Takeda San Diego Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVE SITE; BOTULINUM NEUROTOXINS; NATURAL PRODUCTS; ZINC METALLOPROTEASE;

ZINC;

ACIDS;

BOTULINUM TOXIN A; CAFTARIC ACID; CHLOROGENIC ACID; CICHORIC ACID; HYDROXAMIC ACID DERIVATIVE; METALLOPROTEINASE; METALLOPROTEINASE INHIBITOR; NATURAL PRODUCT; PROTEINASE; SYNAPTOSOMAL ASSOCIATED PROTEIN 25; UNCLASSIFIED DRUG; ZINC METALLOPROTEASE; BIOLOGICAL FACTOR; CAFFEIC ACID DERIVATIVE; HYDROXAMIC ACID; PHENOL DERIVATIVE; PROTEINASE INHIBITOR; SUCCINIC ACID DERIVATIVE;

ALPHA HELIX; AMINO TERMINAL SEQUENCE; ARTICLE; BETA SHEET; BINDING SITE; CARBOXY TERMINAL SEQUENCE; CATALYSIS; CHEMICAL REACTION; CRYSTALLOGRAPHY; DRUG MECHANISM; ECHINACEA; ENZYME ACTIVE SITE; ENZYME INHIBITION; ENZYME SUBSTRATE COMPLEX; HIGH THROUGHPUT SCREENING; IMMUNOPROPHYLAXIS; INTERNALIZATION; INTOXICATION; KINETICS; LIGHT CHAIN; MICHAELIS CONSTANT; MUTAGENESIS; PROTEIN PROTEIN INTERACTION; CHEMISTRY; CLOSTRIDIUM BOTULINUM; CONFORMATION; DRUG ANTAGONISM; ENZYMOLOGY; METABOLISM; STEREOISOMERISM; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

BIOLOGICAL FACTORS; BOTULINUM TOXIN TYPE A; CAFFEIC ACIDS; CHLOROGENIC ACID; CLOSTRIDIUM BOTULINUM; HYDROXAMIC ACIDS; MOLECULAR CONFORMATION; PHENOLS; PROTEASE INHIBITORS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SUCCINATES;

EID: 77950343388     PISSN: 00027863     EISSN: 15205126     Source Type: Journal    
DOI: 10.1021/ja910761y     Document Type: Article

References (17)

1. Burnett, J. C.; Henchal, E. A.; Schmaljohn, A. L.; Bavari, S. Nat. Rev. Drug Discovery 2005, 4, 281-297.
2. Simpson, L. L. Annu. Rev. Pharmacol. Toxicol. 2004, 44, 167-193.
3. Willis, B.; Eubanks, L. M.; Dickerson, T. J.; Janda, K. D. Angew. Chem., Int. Ed. 2008, 47, 8360-8379, and references cited therein.
4. Breidenbach, M. A.; Brunger, A. T. Nature 2004, 432, 925-929.
5. Chen, S.; Barbieri, J. T. J. Biol. Chem. 2006, 281, 10906-10911.
6. (a) Arkin, M. R.; Wells, J. A. Nat. Rev. Drug Discovery 2004, 3, 301-317.
7. (b) Toogood, P. L. J. Med. Chem. 2002, 45, 1543-1558.
8. BoNT/A noncompetitive inhibition has been reported; however, these studies have utilized the small peptide substrate SNAPtide, which is known to produce an inner filter effect confounding mechanistic interpretations, (a) Boldt, G. E.; Kennedy, J. P.; Hixon, M. S.; McAllister, L. A.; Barbieri, J. T.; Tzipori, S.; Janda, K. D. J. Comb. Chem. 2006, 8, 513-521.
9. (b) Cai, S.; Lindo, P.; Park, J.-B.; Vasa, K.; Singh, B. R. Toxicon, in press.
10. (c) Lai, H.; Feng, M.; Roxas-Duncan, V.; Dakshanamurthy, S.; Smith, L. A.; Yang, D. C. H. Arch. Biochem. Biophys. 2009, 491, 75-84.
11. Cheminat, A.; Zawatzky, R.; Becker, H.; Brouillard, R. Phytochemistry 1988, 27, 2787-2794.
12. Boldt, G. E.; Kennedy, J. P.; Janda, K. D. Org. Lett. 2006, 8, 1729-1732.
13. Reinke, R. A.; Lee, D. J.; McDougall, B. R.; King, P. J.; Victoria, J.; Mao, Y.; Lei, X.; Reinecke, M. G.; Robinson, W. E., Jr. Virology 2004, 326, 203-219.
14. C̀apková, K.; Hixon, M. S.; McAllister, L. A.; Janda, K D. Chem. Commun. 2008, 14, 3525-3527.
15. Bock, P. E.; Panizzi, P.; Verhamme, I. M. A. J. Thromb. Haemost. 2007, 5, 81-94.
16. Segel, I. H. Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems; Wiley & Sons: Hoboken, NJ, 1975.
17. Silvaggi, N. R.; Boldt, G. E.; Hixon, M. S.; Kennedy, J. P.; Tzipori, S.; Janda, K. D.; Allen, K N. Chem Biol. 2007, 14, 533-542.