Structural Studies on Intact Clostridium Botulinum Neurotoxins Complexes with Inhibitors Leading to Drug Design
Abstract
In this second annual report we present our progress on three different areas. We are working on intact BoNT/B to identify small molecules that could be used to block the toxic activity. In this respect, we have discovered that two calcium ions are bound to BoNT/B and that at least one of them plays an important role in the translocation of the catalytic domain into the cytosol. We propose that this calcium ion site could be targeted by calcium specific chelators to block translocation. As for the ganglioside binding site as a target, we are working with both intact BoNT/B and structurally similar C fragment of tetanus neurotoxin. We have identified two molecules that might compete with ganglioside for binding which could potentially be used as inhibitor. One of our Statements Of Work is to work with Clostridium botulinum neurotoxin E. Since the diffraction quality of intact toxin is poor, it is difficult to use the intact toxin for inhibitor study via x-ray crystallography. We are using BoNT/E light chain to this inhibitor study and have determined the crystal structure of BoNT/E light.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2004
- Accession Number
- ADA422765
Entities
People
- Subramanyam Swaminathan
Organizations
- Brookhaven National Laboratory