1I1E

CRYSTAL STRUCTURE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN B COMPLEXED WITH DOXORUBICIN

Summary for 1I1E

• Entry DOI: 10.2210/pdb1i1e/pdb
• Related: 1epw 1f31 1g9a
• Descriptor: BOTULINUM NEUROTOXIN TYPE B, DOXORUBICIN, ZINC ION, ... (5 entities in total)
• Functional Keywords: botulinum, neurotoxin, metalloprotease, complex, doxorubicin, hydrolase
• Biological source: Clostridium botulinum
• Cellular location: Botulinum neurotoxin B light chain: Secreted. Botulinum neurotoxin B heavy chain: Secreted: P10844
• Total number of polymer chains: 1
• Total formula weight: 151538.37

Authors

Eswaramoorthy, S.,Kumaran, D.,Swaminathan, S. (deposition date: 2001-02-01, release date: 2001-11-21, Last modification date: 2024-10-30)

Primary citation

Eswaramoorthy, S.,Kumaran, D.,Swaminathan, S.
Crystallographic evidence for doxorubicin binding to the receptor-binding site in Clostridium botulinum neurotoxin B.
Acta Crystallogr.,Sect.D, 57:1743-1746, 2001

PubMed Abstract: 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.

PubMed: 11679763
DOI: 10.1107/S0907444901013531

Experimental method

X-RAY DIFFRACTION (2.5 Å)