Taxonomic group: bacteria / Firmicutes
(Phylum: Firmicutes)
Host organism: (mammal)
Organ / tissue: neuronsAssociated disease: botulism [ICD11:
1A11 
, ICD11:
XN2JN ];
infection due to Clostridium botulinum [ICD11:
XN2JN ]
NCBI PubMed ID: 11679763Publication DOI: 10.1107/S0907444901013531Journal NLM ID: 9305878Publisher: Malden, MA: Wiley-Blackwell
Institutions: Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA
The neurotoxins of Clostridium botulinum and tetanus bind to gangliosides as a first step of their toxin activity. Identifying suitable receptors that compete with gangliosides could prevent toxin binding to the neuronal cells. A possible ganglioside-binding site of the botulinum neurotoxin B (BoNT/B) has already been proposed and evidence is now presented for a drug binding to botulinum neurotoxin B from structural studies. Doxorubicin, a well known DNA intercalator, binds to the neurotoxin at the receptor-binding site proposed earlier. The structure of the BoNT/B-doxorubicin complex reveals that doxorubicin has interactions with the neurotoxin similar to those of sialyllactose. The aglycone moiety of the doxorubicin stacks with tryptophan 1261 and interacts with histidine 1240 of the binding domain. Here, the possibility is presented of designing a potential antagonist for these neurotoxins from crystallographic analysis of the neurotoxin-doxorubicin complex, which will be an excellent lead compound.
Bacterial Proteins, chemistry, DNA, analysis, molecular, X-ray, gangliosides, proteins, models, Clostridium, Crystallography, Binding Sites, toxins, Clostridium botulinum, Crystallization, Protein Conformation, neurotoxin B, botulism, doxorubicin, Botulinum Toxins, Histidine, Neurotoxins, Tryptophan
Structure type: monomer
Location inside paper: Fig. 1
Aglycon: (->10) (8S,10S)-6,8,10,11-tetrahydroxy-8-(2-hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione
Trivial name: daunosamine glycoside, doxorubicin
Compound class: ganglioside mimics
Methods: crystallographic methods
Biological activity: anti-cancer, antibiotic, DNA-intercalator
Biosynthesis and genetic data: binds to botulinum Neurotoxin B
Comments, role: complex of neurotoxin and doxorubicin.
NCBI Taxonomy refs (TaxIDs): 1491Reference(s) to other database(s): GTC:G37034AQ, KEGG:
D03899, CA-RN:23214-92-8
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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