Structural Genomics of Bacterial Virulence Factors
Abstract
We are applying a comprehensive yet focused structural genomics approach to determine the atomic resolution crystal structures of key bacterial virulence factors from high priority bacterial pathogens. Knowledge of protein structure and inhibitor complexes at atomic resolution is typically a pre-requisite for rational drug design. In this first year of funding we have focused our attention on plasmid annotation, target selection, protein expression, purification and crystallization of proteins encoded by the Bacillus anthracis pXOl plasmid. We have cloned and expressed a total of 35 new proteins, and structural analysis of several of these is underway. Currently, 3 new crystal structures are essentially complete, and 6 crystal structures of anthrax Lethal Factor in complex with small molecule inhibitors provided by our collaborators have been determined, and lodged in the public data base. We have also determined the first crystal structure of a complex between anthrax protective Antigen and its host cell receptor. The work performed under this grant has allowed us to leverage funding in several NIAID-funded research projects to carry out in-depth structure-function studies that will enable the next stages of drug design.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA425660
Entities
People
- Robert C. Liddington
Organizations
- Sanford Burnham Prebys Medical Discovery Institute