CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN SEROTYPE B.
Book
·
OSTI ID:789785
- BROOKHAVEN NATIONAL LABORATORY
The toxigenic strains of Clostridium botulinum produce seven serologically distinct types of neurotoxins labeled A - G (EC 3.4.24.69), while Clostridium tetani produces tetanus neurotoxin (EC 3.4.24.68). Botulinum and tetanus neurotoxins (BoNTs and TeNT) are produced as single inactive chains of molecular mass of approximately 150 kDa. Most of these neurotoxins are released after being cleaved into two chains, a heavy chain (HI) of 100 kDa and a light chain (L) of 50 kDa held together by an interchain disulfide bond, by tissue proteinases. BoNT/E is released as a single chain but cleaved by host proteinases [1]. Clostvidium botulinum neurotoxins are extremely poisonous proteins with their LD{sub 50} for humans in the range of 0.1 - 1 ng kg{sup -1} [2]. Botulinum neurotoxins are responsible for neuroparalytic syndromes of botulism characterized by serious neurological disorders and flaccid paralysis. BoNTs block the release of acetylcholine at the neuromuscular junction causing flaccid paralysis while TeNT blocks the release of neurotransmitters like glycine and {gamma}-aminobutyric acid (GABA) in the inhibitory interneurons of the spinal cord resulting in spastic paralysis. In spite of different clinical symptoms, their aetiological agents intoxicate neuronal cells in the same way and these toxins have similar structural organization [3].
- Research Organization:
- Brookhaven National Lab., Upton, NY (US)
- Sponsoring Organization:
- USDOE Office of Energy Research (ER) (US)
- DOE Contract Number:
- AC02-98CH10886
- OSTI ID:
- 789785
- Report Number(s):
- BNL--68838; NN2004000; NN2004000
- Country of Publication:
- United States
- Language:
- English
Similar Records
Structural And Biochemical Studies of Botulinum Neurotoxin Serotype C1 Light Chain Protease: Implications for Dual Substrate Specificity
Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling
Substrate Binding Mode and its Implication on Drug Design for Botulinum Neurotoxin A
Journal Article
·
Mon Jun 01 00:00:00 EDT 2009
· Biochem. 46:10685,2007
·
OSTI ID:953998
Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystal structures, structure-activity relationship and pharmacophore modeling
Journal Article
·
Tue May 01 00:00:00 EDT 2012
· Acta Crystallographica D: Biological Crystallography
·
OSTI ID:1049235
Substrate Binding Mode and its Implication on Drug Design for Botulinum Neurotoxin A
Journal Article
·
Mon Dec 31 23:00:00 EST 2007
· PLoS Pathogens
·
OSTI ID:980578