Abstract: The immediate goals of the contract on the structure and function relationship of botulinum neurotoxin are: 1) Determine the three-dimensional structure of botulinum neurotoxin at atomic resolution by x-ray crystallography. 2) Based on the structure of the neurotoxin, understand the toxins mechanism of action. We have accomplished the first goal of determining the three-dimensional structure of the 150 kD botulinum neurotoxin serotype A. The toxin is Y-shaped, with a very long alpha-helical translocation domain forming the backbone of the structure. The translocation domain is composed almost entirely of helices, 2 of which are 95 A in length and form a pseudo-coiled coil. The binding domain and catalytic domain are more globular in shape, located at two different ends of the translocation domain. The overall dimensions of the protein are 120 A x 80 A x 40 A. A complete description of the three- dimensional structure is described in the report (the manuscript will he published in the September issue of Nature Structural Biology). We have recently collected data on an inhibitor complex and a receptor - complex. Refinement and analysis of the toxin with bound molecules will be completed within the next 12 months.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual rept. 1 Aug 97-30 Jun 98 |
| Pages: |
60 |
| Report Date: |
JUL 1998 |
| Contract Number: |
DAMD17-93-C-3118 |
| Report Number: |
A181553 |
|
|
|
|
Keywords relating to this report:
