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Abstract:
We are continuing to apply a comprehensive but focused structural genomics approach to determine the atomic resolution crystal structures of key virulence factors from high priority pathogens. The work in our first year focused on proteins encoded by the B. anthracis virulence plasmid, pXOl, and the setting up of a virulence factor computational data base. In the second year we expanded our efforts to include genome-encoded proteins of B. anthracis, structural studies on proteins encoded by Variola virus, thecausative agent of smallpox; initiated work to characterize a SARS virus surface protein in complex with a neutralizing antibody; and inititated work on a close homolog of a Yersinia pestis SuMoylase. We have generated a large library of expression vectors for virulence factors, as well as research quantities of pure proteins, which could readily be adapted for vaccine design. In the broader and longer term, the accumulated structural information will generate important and testable hypotheses that will increase our understanding of the molecular mechanisms of pathogenicity, putting us in a stronger position to anticipate and react to emerging pathogens.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual rept. 1 May 2004-30 Apr 2005 |
| Pages: |
118 |
| Report Date: |
MAY 2005 |
| Contract Number: |
DAMD170320038 |
| Report Number: |
A747064 |
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