A Potent Peptidomimetic Inhibitor of Botulinum Neurotoxin Serotype A Has a Very Different Conformation than SNAP-25 Substrate

Structure

Volumn 16, Issue 10, 2008, Pages 1588-1597

  Zuniga, Jorge E ^a   Schmidt, James J ^b   Fenn, Timothy ^a   Burnett, James C ^c   Araç, Demet ^a   Gussio, Rick ^d   Stafford, Robert G ^b   Badie, Shirin S ^b   Bavari, Sina ^b   Brunger, Axel T ^a  

^a STANFORD UNIVERSITY   (United States)

^b UNITED STATES ARMY MEDICAL RESEARCH INSTITUTE OF INFECTIOUS DISEASES   (United States)

^c SAIC FREDERICK INC   (United States)

^d NATIONAL CANCER INSTITUTE   (United States)

Author keywords

MOLNEURO; PROTEINS

Indexed keywords

ANTITOXIN; BOTULINUM A ANTITOXIN; BOTULINUM TOXIN A; PSEUDOPEPTIDE; SYNAPTOSOMAL ASSOCIATED PROTEIN 25; THERMOLYSIN; UNCLASSIFIED DRUG; WATER;

AMINO ACID SEQUENCE; ARTICLE; BINDING AFFINITY; BINDING SITE; CATALYSIS; CRYSTAL STRUCTURE; DRUG SPECIFICITY; DRUG STRUCTURE; ENZYME BINDING; ENZYME CONFORMATION; INHIBITION KINETICS; MOLECULE; PEPTIDOMICS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; SEQUENCE HOMOLOGY;

AMINO ACID SEQUENCE; BINDING SITES; BIOMIMETICS; BOTULINUM TOXIN TYPE A; DRUG EVALUATION, PRECLINICAL; MODELS, BIOLOGICAL; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PEPTIDE FRAGMENTS; PROTEIN BINDING; PROTEIN CONFORMATION; SUBSTRATE SPECIFICITY; SYNAPTOSOMAL-ASSOCIATED PROTEIN 25;

EID: 53249152019     PISSN: 09692126     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.str.2008.07.011     Document Type: Article

References (27)

1. Adams P.D., Grosse-Kunstleve R.W., Hung L.W., Ioerger T.R., McCoy A.J., Moriarty N.W., Read R.J., Sacchettini J.C., Sauter N.K., and Terwilliger T.C. PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr. D Biol. Crystallogr. 58 (2002) 1948-1954
2. Agarwal R., Eswaramoorthy S., Kumaran D., Binz T., and Swaminathan S. Structural analysis of botulinum neurotoxin type E catalytic domain and its mutant Glu212→Gln reveals the pivotal role of the Glu212 carboxylate in the catalytic pathway. Biochemistry 43 (2004) 6637-6644
3. Binz T., Bade S., Rummel A., Kollewe A., and Alves J. Arg(362) and Tyr(365) of the botulinum neurotoxin type a light chain are involved in transition state stabilization. Biochemistry 41 (2002) 1717-1723
4. Blasi J., Chapman E.R., Link E., Binz T., Yamasaki S., De Camilli P., Sudhof T.C., Niemann H., and Jahn R. Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. Nature 365 (1993) 160-163
5. Blasi J., Chapman E.R., Yamasaki S., Binz T., Niemann H., and Jahn R. Botulinum neurotoxin C1 blocks neurotransmitter release by means of cleaving HPC-1/syntaxin. EMBO J. 12 (1993) 4821-4828
6. Boldt G.E., Kennedy J.P., and Janda K.D. Identification of a potent botulinum neurotoxin a protease inhibitor using in situ lead identification chemistry. Org. Lett. 8 (2006) 1729-1732
7. Breidenbach M.A., and Brunger A.T. Substrate recognition strategy for botulinum neurotoxin serotype A. Nature 432 (2004) 925-929
8. Burnett J.C., Ruthel G., Stegmann C.M., Panchal R.G., Nguyen T.L., Hermone A.R., Stafford R.G., Lane D.J., Kenny T.A., McGrath C.F., et al. Inhibition of metalloprotease botulinum serotype A from a pseudo-peptide binding mode to a small molecule that is active in primary neurons. J. Biol. Chem. 282 (2007) 5004-5014
9. Davis I.W., Leaver-Fay A., Chen V.B., Block J.N., Kapral G.J., Wang X., Murray L.W., Arendall III W.B., Snoeyink J., Richardson J.S., and Richardson D.C. MolProbity: all-atom contacts and structure validation for proteins and nucleic acids. Nucleic Acids Res. 35 (2007) W375-W383
10. Emsley P., and Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60 (2004) 2126-2132
11. Fu Z., Chen S., Baldwin M.R., Boldt G.E., Crawford A., Janda K.D., Barbieri J.T., and Kim J.J. Light chain of botulinum neurotoxin serotype A: structural resolution of a catalytic intermediate. Biochemistry 45 (2006) 8903-8911
12. Josko D. Botulin toxin: a weapon in terrorism. Clin. Lab. Sci. 17 (2004) 30-34
13. Kukreja R., and Singh B. Biologically active novel conformational state of botulinum, the most poisonous poison. J. Biol. Chem. 280 (2005) 39346-39352
14. Kumaran D., Rawat R., Ludivico M.L., Ahmed S.A., and Swaminathan S. Structure- and substrate-based inhibitor design for Clostridium botulinum neurotoxin serotype A. J Biol. Chem. 283 (2008) 18883-18891
15. Lacy D.B., Tepp W., Cohen A.C., DasGupta B.R., and Stevens R.C. Crystal structure of botulinum neurotoxin type A and implications for toxicity. Nat. Struct. Biol. 5 (1998) 898-902
16. Li L., Binz T., Niemann H., and Singh B.R. Probing the mechanistic role of glutamate residue in the zinc-binding motif of type A botulinum neurotoxin light chain. Biochemistry 39 (2000) 2399-2405
17. McCoy A.J., Grosse-Kunstleve R.W., Storoni L.C., and Read R.J. Likelihood-enhanced fast translation functions. Acta Crystallogr. D Biol. Crystallogr. 61 (2005) 458-464
18. Otwinowski Z., and Minor W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276 (1997) 307-326
19. Rao B.G. Recent developments in the design of specific Matrix Metalloproteinase inhibitors aided by structural and computational studies. Curr. Pharm. Des. 11 (2005) 295-322
20. Schiavo G., Benfenati F., Poulain B., Rossetto O., Polverino de Laureto P., DasGupta B.R., and Montecucco C. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 359 (1992) 832-835
21. Schmidt J.J., and Bostian K.A. Endoproteinase activity of type A botulinum neurotoxin: substrate requirements and activation by serum albumin. J. Protein Chem. 16 (1997) 19-26
22. Schmidt J.J., Stafford R.G., and Bostian K.A. Type A botulinum neurotoxin proteolytic activity: development of competitive inhibitors and implications for substrate specificity at the S1′ binding subsite. FEBS Lett. 435 (1998) 61-64
23. Segel I.H. Enzyme kinetics: behavior and analysis of rapid equilibrium and steady state enzyme systems (1975), Wiley, New York
24. Silvaggi N.R., Boldt G.E., Hixon M.S., Kennedy J.P., Tzipori S., Janda K.D., and Allen K.N. Structures of Clostridium botulinum neurotoxin serotype A light chain complexed with small-molecule inhibitors highlight active-site flexibility. Chem. Biol. 14 (2007) 533-542
25. Silvaggi N.R., Wilson D., Tzipori S., and Allen K.N. Catalytic features of the botulinum neurotoxin A light chain revealed by high resolution structure of an inhibitory peptide complex. Biochemistry 47 (2008) 5736-5745
26. Suzuki T., and Miyata N. Non-hydroxamate histone deacetylase inhibitors. Curr. Med. Chem. 12 (2005) 2867-2880
27. Swaminathan S., Eswaramoorthy S., and Kumaran D. Structure and enzymatic activity of botulinum neurotoxins. Mov. Disord. 19 Suppl 8 (2004) S17-S22