Disulfide bond reduction corresponds to dimerization and hydrophobicity changes of Clostridium botulinum type A neurotoxin
| Autor: | Jiunn-Jye Wey, Tzong-Yuan Wu, Shiao-Shek Tang |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Stereochemistry
Clostridium botulinum type A Crystallography X-Ray medicine.disease_cause Ion Channels chemistry.chemical_compound Clostridium botulinum medicine Organic chemistry Neurotoxin Pharmacology (medical) Disulfides Botulinum Toxins Type A Protein Structure Quaternary Pharmacology Ligand binding assay General Medicine Hydrogen-Ion Concentration Monomer Membrane Sulfonate chemistry Protein quaternary structure Dimerization Hydrophobic and Hydrophilic Interactions |
| Zdroj: | Acta Pharmacologica Sinica. 27:1238-1246 |
| ISSN: | 1745-7254 1671-4083 |
| DOI: | 10.1111/j.1745-7254.2006.00372.x |
| Popis: | Aim: To determine the structure factors that mediate the intoxication process of botulinum neurotoxin type A (BoNT/A). Methods: Triton X-114 phase separation experiments and 1-anilino-8-naphthalene sulfonate binding assay were used to study the structural factor that corresponds to the hydrophobicity change of BoNT/A. In addition, sucrose density gradient centrifugation and a chemical crosslinking study were employed to determine the quaternary structure of BoNT/ A. Results: Our results demonstrated that in other than acidic conditions, the disulfide reduction is the structural factor that corresponds to the hydrophobicity change of BoNT/A. The quaternary structure of BoNT/A exists as a dimmer in acidic solution (pH 4.5), although the monomeric structure of BoNT/A was reported based on X-ray crystallography. Conclusion: Disulfide bond reduction is critical for BoNT/A's channel formation and ability to cross endosome membranes. This result implies that compounds that block this disulfide bond reduction may serve as potential therapeutic agents for botulism. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text