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Structural analysis of botulinum neurotoxin serotype F light chain: implications on substrate binding and inhibitor design.

Agarwal R, Binz T, Swaminathan S
Biochemistry 44 11758-65 (2005)
Cited: 47 times
EuropePMC logo PMID: 16128577

Abstract

The seven serologically distinct Clostridium botulinum neurotoxins (BoNTs A-G) are zinc endopeptidases which block the neurotransmitter release by cleaving one of the three proteins of the soluble N-ethylmaleimide-sensitive-factor attachment protein receptor complex (SNARE complex) essential for the fusion of vesicles containing neurotransmitters with target membranes. These metallopeptidases exhibit unique specificity for the substrates and peptide bonds they cleave. Development of countermeasures and therapeutics for BoNTs is a priority because of their extreme toxicity and potential misuse as biowarfare agents. Though they share sequence homology and structural similarity, the structural information on each one of them is required to understand the mechanism of action of all of them because of their specificity. Unraveling the mechanism will help in the ultimate goal of developing inhibitors as antibotulinum drugs for the toxins. Here, we report the high-resolution structure of active BoNT/F catalytic domain in two crystal forms. The structure was exploited for modeling the substrate binding and identifying the S1' subsite and the putative exosites which are different from BoNT/A or BoNT/B. The orientation of docking of the substrate at the active site is consistent with the experimental BoNT/A-LC:SNAP-25 peptide model and our proposed model for BoNT/E-LC:SNAP-25.

Articles - 2a97 mentioned but not cited (12)

  1. Immunological Characterization and Neutralizing Ability of Monoclonal Antibodies Directed Against Botulinum Neurotoxin Type H. Fan Y, Barash JR, Lou J, Conrad F, Marks JD, Arnon SS. J Infect Dis 213 1606-1614 (2016)
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  5. Structural framework for covalent inhibition of Clostridium botulinum neurotoxin A by targeting Cys165. Stura EA, Le Roux L, Guitot K, Garcia S, Bregant S, Beau F, Vera L, Collet G, Ptchelkine D, Bakirci H, Dive V. J Biol Chem 287 33607-33614 (2012)
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  7. Structural and biochemical characterization of the protease domain of the mosaic botulinum neurotoxin type HA. Lam KH, Sikorra S, Weisemann J, Maatsch H, Perry K, Rummel A, Binz T, Jin R. Pathog Dis 76 (2018)
  8. Precipitation during Quenching in 2A97 Aluminum Alloy and the Influences from Grain Structure. Wang X, Jiang J, Li G, Shao W, Zhen L. Materials (Basel) 14 2802 (2021)
  9. Crystal Structure of the Catalytic Domain of a Botulinum Neurotoxin Homologue from Enterococcus faecium: Potential Insights into Substrate Recognition. Gregory KS, Hall PR, Onuh JP, Mojanaga OO, Liu SM, Acharya KR. Int J Mol Sci 24 12721 (2023)
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Reviews citing this publication (12)

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  7. Translocation of botulinum neurotoxin light chain protease by the heavy chain protein-conducting channel. Montal M. Toxicon 54 565-569 (2009)
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Articles citing this publication (23)

  1. Crucial role of the disulfide bridge between botulinum neurotoxin light and heavy chains in protease translocation across membranes. Fischer A, Montal M. J Biol Chem 282 29604-29611 (2007)
  2. Structures of Clostridium botulinum Neurotoxin Serotype A Light Chain complexed with small-molecule inhibitors highlight active-site flexibility. Silvaggi NR, Boldt GE, Hixon MS, Kennedy JP, Tzipori S, Janda KD, Allen KN. Chem Biol 14 533-542 (2007)
  3. Mechanism of substrate recognition by botulinum neurotoxin serotype A. Chen S, Kim JP, Barbieri JT. J Biol Chem 282 9621-9627 (2007)
  4. Botulinum neurotoxin heavy chain belt as an intramolecular chaperone for the light chain. Brunger AT, Breidenbach MA, Jin R, Fischer A, Santos JS, Montal M. PLoS Pathog 3 1191-1194 (2007)
  5. Bimodal modulation of the botulinum neurotoxin protein-conducting channel. Fischer A, Nakai Y, Eubanks LM, Clancy CM, Tepp WH, Pellett S, Dickerson TJ, Johnson EA, Janda KD, Montal M. Proc Natl Acad Sci U S A 106 1330-1335 (2009)
  6. Regulation of error-prone translesion synthesis by Spartan/C1orf124. Kim MS, Machida Y, Vashisht AA, Wohlschlegel JA, Pang YP, Machida YJ. Nucleic Acids Res 41 1661-1668 (2013)
  7. Mode of VAMP substrate recognition and inhibition of Clostridium botulinum neurotoxin F. Agarwal R, Schmidt JJ, Stafford RG, Swaminathan S. Nat Struct Mol Biol 16 789-794 (2009)
  8. Structure- and substrate-based inhibitor design for Clostridium botulinum neurotoxin serotype A. Kumaran D, Rawat R, Ludivico ML, Ahmed SA, Swaminathan S. J Biol Chem 283 18883-18891 (2008)
  9. Molecular architecture of botulinum neurotoxin E revealed by single particle electron microscopy. Fischer A, Garcia-Rodriguez C, Geren I, Lou J, Marks JD, Nakagawa T, Montal M. J Biol Chem 283 3997-4003 (2008)
  10. Identification of residues surrounding the active site of type A botulinum neurotoxin important for substrate recognition and catalytic activity. Ahmed SA, Olson MA, Ludivico ML, Gilsdorf J, Smith LA. Protein J 27 151-162 (2008)
  11. Quinolinol and peptide inhibitors of zinc protease in botulinum neurotoxin A: effects of zinc ion and peptides on inhibition. Lai H, Feng M, Roxas-Duncan V, Dakshanamurthy S, Smith LA, Yang DC. Arch Biochem Biophys 491 75-84 (2009)
  12. Different substrate recognition requirements for cleavage of synaptobrevin-2 by Clostridium baratii and Clostridium botulinum type F neurotoxins. Kalb SR, Baudys J, Egan C, Smith TJ, Smith LA, Pirkle JL, Barr JR. Appl Environ Microbiol 77 1301-1308 (2011)
  13. Specificity of botulinum protease for human VAMP family proteins. Yamamoto H, Ida T, Tsutsuki H, Mori M, Matsumoto T, Kohda T, Mukamoto M, Goshima N, Kozaki S, Ihara H. Microbiol Immunol 56 245-253 (2012)
  14. A capillary electrophoresis method to assay catalytic activity of botulinum neurotoxin serotypes: implications for substrate specificity. Purcell AL, Hoard-Fruchey HM. Anal Biochem 366 207-217 (2007)
  15. SNAP-25 substrate peptide (residues 180-183) binds to but bypasses cleavage by catalytically active Clostridium botulinum neurotoxin E. Agarwal R, Swaminathan S. J Biol Chem 283 25944-25951 (2008)
  16. Augmentation of VAMP-catalytic activity of botulinum neurotoxin serotype B does not result in increased potency in physiological systems. Elliott M, Maignel J, Liu SM, Favre-Guilmard C, Mir I, Farrow P, Hornby F, Marlin S, Palan S, Beard M, Krupp J. PLoS One 12 e0185628 (2017)
  17. Catch and Anchor Approach To Combat Both Toxicity and Longevity of Botulinum Toxin A. Lin L, Olson ME, Sugane T, Turner LD, Tararina MA, Nielsen AL, Kurbanov EK, Pellett S, Johnson EA, Cohen SM, Allen KN, Janda KD. J Med Chem 63 11100-11120 (2020)
  18. High level expression of the light chain of botulinum neurotoxin serotype C1 and an efficient HPLC assay to monitor its proteolytic activity. Rawat R, Ashraf Ahmed S, Swaminathan S. Protein Expr Purif 60 165-169 (2008)
  19. Epitope characterization and variable region sequence of f1-40, a high-affinity monoclonal antibody to botulinum neurotoxin type a (Hall strain). Scotcher MC, McGarvey JA, Johnson EA, Stanker LH. PLoS One 4 e4924 (2009)
  20. Structure and activity of a functional derivative of Clostridium botulinum neurotoxin B. Masuyer G, Beard M, Cadd VA, Chaddock JA, Acharya KR. J Struct Biol 174 52-57 (2011)
  21. Tyrosine phosphorylation of botulinum neurotoxin protease domains. Toth S, Brueggmann EE, Oyler GA, Smith LA, Hines HB, Ahmed SA. Front Pharmacol 3 102 (2012)
  22. Comparative Genomics of Clostridium baratii Reveals Strain-Level Diversity in Toxin Abundance. Silva-Andrade C, Martin AJ, Garrido D. Microorganisms 10 213 (2022)
  23. Molecular biology of botulinum neurotoxin serotype A: a cosmetic perspective. Eapen BR. J Cosmet Dermatol 7 221-225 (2008)


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