Structural Studies on Intact Clostridium Botulinum Neurotoxins Complexed with Inhibitors Leading to Drug Design

Abstract

In this fourth annual report we present our progress on several fronts. We have identified a number of inactive mutants of BoNT/E-LC which may be potentially used as vaccine candidates. Crystal structures of several catalytic domains of clostridial neurotoxins have been determined and it has been shown that there is a commonality of the architecture of the active site. Accordingly it must be possible to design a common drug for all of them. We have determined the structure of the C fragment of botulinum neurotoxin type B and found that the N-terminal helix reorients. Virtual screening with small molecule library has been successfully carried out with BoNT/E-LC. The C fragment of BoNT/A has been successfully cloned and expressed.

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Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2006
Accession Number
ADA466700

Entities

People

  • Subramanyam Swaminathan

Organizations

  • Brookhaven National Laboratory

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Cells
  • Chemistry
  • Crystal Structure
  • Crystals
  • Diffraction
  • Diseases And Disorders
  • Electron Density
  • Fungi
  • Medical Personnel
  • Molecules
  • Peripheral Nervous System
  • Small Molecules
  • Synapses
  • Three Dimensional
  • Vaccines
  • X-Ray Diffraction

Fields of Study

  • Chemistry

Readers

  • Microbial Pathology
  • Molecular and Cellular Biochemistry

Technology Areas

  • Biotechnology