Subsite specificity of anthrax lethal factor and its implications for inhibitor development.

ABSTRACT: The lethal factor of Bacillus anthracis is a major factor for lethality of anthrax infection by this bacterium. With the aid of the protective antigen, lethal factor gains excess to the cell cytosol where it manifests toxicity as a metalloprotease. For better understanding of its specificity, we have determined its residue preferences of 19 amino acids in six subsites (from P3 to P3') as relative k(cat)/K(m) values (specificity constants). These results showed that lethal factor has a broad specificity with preference toward hydrophobic residues, but not charged or branched residues. The most preferred residues in these six subsites are, from P1 to P3', Trp, Leu, Met, Tyr, Pro, and Leu. The result of residue preference was used to design new substrates with superior hydrolytic characterist

SUBMITTER: Li F 

PROVIDER: S-EPMC3104405 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature