Catalytic features of the botulinum neurotoxin A light chain revealed by high resolution structure of an inhibitory peptide complex

Biochemistry

Volumn 47, Issue 21, 2008, Pages 5736-5745

  Silvaggi, Nicholas R ^a   Wilson, David ^b   Tzipori, Saul ^c   Allen, Karen N ^a,d  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c TUFTS UNIVERSITY   (United States)

^d NONE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CATALYST ACTIVITY; COMPLEXATION; TOXIC MATERIALS;

BOTULINUM NEUROTOXIN A; EXOCYTOSIS;

PEPTIDES;

ACETYLCHOLINE; BOTULINUM TOXIN A; CYSTEINE; METAL ION; OXYGEN; SNARE PROTEIN; SULFUR; SYNAPTOSOMAL ASSOCIATED PROTEIN 25; ZINC;

ARTICLE; CATALYSIS; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; ENZYME MECHANISM; ENZYME STABILITY; LIGHT CHAIN; NONHUMAN; OPTICAL RESOLUTION; OXIDATION; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN STRUCTURE; X RAY DIFFRACTION;

ACETYLCHOLINE; BOTULINUM TOXIN TYPE A; CATALYSIS; CATALYTIC DOMAIN; CYSTEINE; IONS; KINETICS; LIGHT; MODELS, MOLECULAR; MOLECULAR CONFORMATION; OXYGEN; PEPTIDES; PROTEIN CONFORMATION; SULFENIC ACIDS; ZINC;

CLOSTRIDIUM BOTULINUM;

EID: 44349178037     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi8001067     Document Type: Article

References (61)

1. Hambleton, P. (1992) Clostridium botulinum toxins: a general review of involvement in disease, structure, mode of action and preparation for clinical use. J. Neurol. 239, 16-20.
2. Hanson, D. (2004) Botulinum toxin: a bioterrorism weapon. Emerg. Med. Serv. 33, 55-59.
3. Josko, D. (2004) Botulin toxin: a weapon in terrorism. Clin. Lab. Sci. 17, 30-34.
4. Patocka, J., Splino, M., and Merka, V. (2005) Botulism and bioterrorism: how serious is this problem? Acta Medica (Hradec Kralove) 48, 23-28.
5. Wein, L. M., and Liu, Y. (2005) Analyzing a bioterror attack on the food supply: the case of botulinum toxin in milk. Proc. Natl. Acad. Sci. U.S.A. 102, 9984-9989.
6. Ansiaux, R., Baudelet, C., Cron, G. O., Segers, J., Dessy, C., Martinive, P., De Wever, J., Verrax, J., Wauthier, V., Beghein, N., Gregoire, V., Buc Calderon, P., Feron, O., and Gallez, B. (2006) Botulinum toxin potentiates cancer radiotherapy and chemotherapy. Clin. Cancer Res. 12, 1276-1283.
7. Costa, J., Espirito-Santo, C., Borges, A., Ferreira, J. J., Coelho, M., Moore, P., and Sampaio, C. (2005) Botulinum toxin type A therapy for cervical dystonia. Cochrane Database Syst. Rev. CD003633.
8. Klaphajone, J., Kitisomprayoonkul, W., and Sriplakit, S. (2005) Botulinum toxin type A injections for treating neurogenic detrusor overactivity combined with low-compliance bladder in patients with spinal cord lesions. Arch. Phys. Med. Rehabil. 86, 2114-2118.
9. Ojala, T., Arokoski, J. P., and Partanen, J. (2006) The effect of small doses of botulinum toxin a on neck-shoulder myofascial pain syndrome: a double-blind, randomized, and controlled crossover trial. Clin. J. Pain. 22, 90-96.
10. Turton, K., Chaddock, J. A., and Acharya, K. R. (2002) Botulinum and tetanus neurotoxins: structure, function and therapeutic utility. Trends Biochem. Sci. 27, 552-558.
11. Lacy, D. B., and Stevens, R. C. (1999) Sequence homology and structural analysis of the clostridial neurotoxins. J. Mol. Biol. 291, 1091-1104.
12. Fischer, A., and Montal, M. (2007) Crucial role of the disulfide bridge between botulinum neurotoxin light and heavy chains in protease translocation across membranes. J. Biol. Chem. 282, 29604-29611.
13. Dong, M., Richards, D. A., Goodnough, M. C., Tepp, W. H., Johnson, E. A., and Chapman, E. R. (2003) Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells. J. Cell Biol. 162, 1293-1303.
14. Jayaraman, S., Eswaramoorthy, S., Ahmed, S. A., Smith, L. A., and Swaminathan, S. (2005) N-terminal helix reorients in recombinant C-fragment of Clostridium botulinum type B. Biochem. Biophys. Res. Commun. 330, 97-103.
15. Lalli, G., Herreros, J., Osborne, S. L., Montecucco, C., Rossetto, O., and Schiavo, G. (1999) Functional characterisation of tetanus and botulinum neurotoxins binding domains. J. Cell. Sci. 112 (Pt 16), 2715-2724.
16. Finkelstein, A. (1990) Channels formed in phospholipid bilayer membranes by diphtheria, tetanus, botulinum and anthrax toxin. J. Physiol. (Paris) 84, 188-190.
17. Lacy, D. B., and Stevens, R. C. (1997) Recombinant expression and purification of the botulinum neurotoxin type A translocation domain. Protein. Expression Purif. 11, 195-200.
18. Lacy, D. B., Tepp, W., Cohen, A. C., DasGupta, B. R., and Stevens, R. C. (1998) Crystal structure of botulinum neurotoxin type A and implications for toxicity. Nat. Struct. Biol. 5, 898-902.
19. Morihara, K., Tsuzuki, H., and Oka, T. (1968) Comparison of the specificities of various neutral proteinases from microorganisms. Arch. Biochem. Biophys. 123, 572-588.
20. Breidenbach, M. A., and Brunger, A. T. (2004) Substrate recognition strategy for botulinum neurotoxin serotype A. Nature 432, 925-929.
21. Schmidt, J. J., and Bostian, K. A. (1997) Endoproteinase activity of type A botulinum neurotoxin: substrate requirements and activation by serum albumin. J. Protein Chem. 16, 19-26.
22. Hanson, M. A., and Stevens, R. C. (2000) Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type B at 2.0 A resolution. Nat. Struct. Biol. 7, 687-692.
23. Breidenbach, M. A., and Brunger, A. T. (2005) New insights into clostridial neurotoxin-SNARE interactions. Trends Mol. Med. 11, 377-381.
24. Swaminathan, S., and Eswaramoorthy, S. (2000) Structural analysis of the catalytic and binding sites of Clostridium botulinum neurotoxin B. Nat. Struct. Biol. 7, 693-699.
25. Brunger, A. T., Breidenbach, M. A., Jin, R., Fischer, A., Santos, J. S., and Montal, M. (2007) Botulinum neurotoxin heavy chain belt as an intramolecular chaperone for the light chain. PLoS Pathog. 3, 1191-1194.
26. Burnett, J. C., Schmidt, J. J., Stafford, R. G., Panchal, R. G., Nguyen, T. L., Hermone, A. R., Vennerstrom, J. L., McGrath, C. F., Lane, D. J., Sausville, E. A., Zaharevitz, D. W., Gussio, R., and Bavari, S. (2003) Novel small molecule inhibitors of botulinum neurotoxin A metalloprotease activity. Biochem. Biophys. Res. Commun. 310, 84-93.
27. Boldt, G. E., Kennedy, J. P., and Janda, K. D. (2006) Identification of a potent botulinum neurotoxin A protease inhibitor using in situ lead identification chemistry. Org. Lett. 8, 1729-1732.
28. Park, J. G., Sill, P. C., Makiyi, E. F., Garcia-Sosa, A. T., Millard, C. B., Schmidt, J. J., and Pang, Y. P. (2006) Serotype-selective, small-molecule inhibitors of the zinc endopeptidase of botulinum neurotoxin serotype A. Bioorg. Med. Chem. 14, 395-408.
29. Tang, J., Park, J. G., Millard, C. B., Schmidt, J. J., and Pang, Y. P. (2007) Computer-aided lead optimization: improved small-molecule inhibitor of the zinc endopeptidase of botulinum neurotoxin serotype A. PLoS ONE 2, e761.
30. Washbourne, P., Pellizzari, R., Baldini, G., Wilson, M. C., and Montecucco, C. (1997) Botulinum neurotoxin types A and E require the SNARE motif in SNAP-25 for proteolysis. FEBS Lett. 418, 1-5.
31. Schmidt, J. J., and Stafford, R. G. (2005) Botulinum neurotoxin serotype F: identification of substrate recognition requirements and development of inhibitors with low nanomolar affinity. Biochemistry 44, 4067-4073.
32. Schmidt, J. J., and Bostian, K. A. (1995) Proteolysis of synthetic peptides by type A botulinum neurotoxin. J Protein Chem 14, 703-708.
33. Evans, E. R., Sutton, J. M., Gravett, A., and Shone, C. C. (2005) Analysis of the substrate recognition domain determinants of botulinum type B toxin using phage display. Toxicon 46, 446-453.
34. Chen, S., and Barbieri, J. T. (2006) Unique substrate recognition by botulinum neurotoxins serotypes A and E. J. Biol. Chem.
35. Schmidt, J. J., Stafford, R. G., and Bostian, K. A. (1998) Type A botulinum neurotoxin proteolytic activity: development of competitive inhibitors and implications for substrate specificity at the S1′ binding subsite. FEBS Lett. 435, 61-64.
36. Schmidt, J. J., and Stafford, R. G. (2002) A high-affinity competitive inhibitor of type A botulinum neurotoxin protease activity. FEBS Lett. 532, 423-426.
37. Otwinowski, Z., and Minor, W. (1997) Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326.
38. Collaborative Computational Project (1994) The CCP4 suite: programs for protein crystallography, Acta Crystallogr., Sect. D 50, 760-763.
39. Silvaggi, N. R., Boldt, G. E., Hixon, M. S., Kennedy, J. P., Tzipori, S., Janda, K. D., and Allen, K. N. (2007) Structures of Clostridium botulinum Neurotoxin Serotype A Light Chain complexed with small-molecule inhibitors highlight active-site flexibility. Chem Biol 14, 533-542.
40. 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. (2002) PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr., Sect. D 58, 1948-1954.
41. Emsley, P., and Cowtan, K. (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr., Sect. D 60, 2126-2132.
42. Davis, I. W., Murray, L. W., Richardson, J. S., and Richardson, D. C. (2004) MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes. Nucleic Acids Res. 32, W615-619.
43. 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., Wipf, P., Stahl, A. M., Schmidt, J. J., Gussio, R., Brunger, A. T., and Bavari, S. (2007) 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, 5004-5014.
44. Fu, Z., Chen, S., Baldwin, M. R., Boldt, G. E., Crawford, A., Janda, K. D., Barbieri, J. T., and Kim, J. J. (2006) Light chain of botulinum neurotoxin serotype A: structural resolution of a catalytic intermediate. Biochemistry 45, 8903-8911.
45. Holland, D. R., Hausrath, A. C., Juers, D., and Matthews, B. W. (1995) Structural analysis of zinc substitutions in the active site of thermolysin. Protein Sci. 4, 1955-1965.
46. Simpson, L. L., Maksymowych, A. B., and Hao, S. (2001) The role of zinc binding in the biological activity of botulinum toxin. J. Biol. Chem. 276, 27034-27041.
47. Eswaramoorthy, S., Kumaran, D., Keller, J., and Swaminathan, S. (2004) Role of metals in the biological activity of Clostridium botulinum neurotoxins. Biochemistry 43, 2209-2216.
48. Claiborne, A., Miller, H., Parsonage, D., and Ross, R. P. (1993) Protein-sulfenic acid stabilization and function in enzyme catalysis and gene regulation. FASEB J. 7, 1483-1490.
49. Atmane, N., Dairou, J., Paul, A., Dupret, J.-M., and Rodrigues-Lima, F. (2003) Redox regulation of the human xenobiotic metabolizing enzyme arylamine N-acetyltransferase 1 (NAT1): reversible inactivation by hydrogen peroxide. J. Biol. Chem. 278, 35086-35092.
50. Seth, D., and Rudolph, J. (2006) Redox regulation of MAP kinase phosphatase 3. Biochemistry 45, 8476-8487.
51. Poole, L. B. (2005) Bacterial defenses against oxidants: mechanistic features of cysteine-based peroxidases and their flavoprotein reductases. Arch. Biochem. Biophys. 433, 240-254.
52. Shetty, V., Spellman, D. S., and Neubert, T. A. (2007) Characterization by tandem mass spectrometry of stable cysteine sulfenic acid in a cysteine switch peptide of matrix metalloproteinases. J. Am. Soc. Mass Spectrom. 18, 1544-1551.
53. Hoffman, J. T., and Carrano, C. J. (2006) S versus O alkylation and coordination in zinc complexes containing the bulky heteroscorpionate alkoxy ligand bis(3,5-dimethylpyrazol-2-yl) diphenylmethanol. Inorg. Chim. Acta 359, 1248-1254.
54. Chakrabarti, P. (1989) Geometry of interaction of metal ions with sulfur-containing ligands in protein structures. Biochemistry 28, 6081-6085.
55. Binz, T., Bade, S., Rummel, A., Kollewe, A., and Alves, J. (2002) Arg(362) and Tyr(365) of the botulinum neurotoxin type a light chain are involved in transition state stabilization. Biochemistry 41, 1717-1723.
56. Evans, S. A., and Shore, J. D. (1980) The role of zinc-bound water in liver alcohol dehydrogenase catalysis. J. Biol. Chem. 255, 1509-1514.
57. Krebs, J. F., and Fierke, C. A. (1993) Determinants of catalytic activity and stability of carbonic anhydrase II as revealed by random mutagenesis. J. Biol. Chem. 268, 948-954.
58. Lunin, V. Y., Afonine, P. V., and Urzhumtsev, A. G. (2002) Likelihood-based refinement. I. Irremovable model errors. Acta Crystallogr. Sect. A 58, 270-282.
59. Holden, H. M., Tronrud, D. E., Monzingo, A. F., Weaver, L. H., and Matthews, B. W. (1987) Slow- and fast-binding inhibitors of thermolysin display different modes of binding: crystallographic analysis of extended phosphonamidate transition-state analogs. Biochemistry 26, 8542-8553.
60. Fenn, T. D., Ringe, D., and Petsko, G. A. (2003) POVScript+: a program for model and data visualization using persistence of vision ray-tracing. J. Appl. Crystallogr. 36, 944-947.
61. Kleywegt, G. J., and Jones, T. A. (1999) Software for handling macromolecular envelopes. Acta Crystallogr., Sect. D 55, 941-944.