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Lethal Factor Sequence

"The N-terminal 26 residues are invisible in our electron density maps, and we presume that they are disordered. All other residues are ordered in at least one crystal form. The five sequence repeats are indicated R1–R5. The zinc-coordinating residues are highlighted in red. The sequence of domain I is homologous to the PA-binding domain of oedema factor, and its three-dimensional structure will be similar. For domain II, secondary structure nomenclature matches that of the N-terminal domain of VIP2." Andrew D. Pannifer et al. Nature. 2001. http://www.nature.com/nature/journal/v414/n6860/fig_tab/414229a0_F2.html

Secondary Structure Edit

Secondary structure was predicted using PredictProtein. The results indicate a mostly helical structure (about 75%) with few loops and even fewer beta strands. The solvent accesibility predictor indicated the molecule has 37% buried sequences, 47% exposed sequences, and 16% intermediate sequences. 

Tertiary StructureEdit

The tertiary structure of anthrax lethal factor has been extensively studied primarily to understand its substrate binding to aid drug development. Research indicates very similar tertiary and quaternary structures of lethal factor. There are four distinct domains that each play an integral role in the proteins' toxic effects. Although the domains can be identified based on their funciton, location, and composition, the protein is a single folden unit. Nonetheless the folded protein contains a
Anthrax Lethal Factor Tertiary Structure

Electron density map of anthrax lethal factor domains 2, 3, 4 with substrate bound. Red indicates negative charge, blue indicates positive charge. Image courtesy of http://www.nature.com/nature/journal/v414/n6860/fig_tab/414229a0_F4.html

zinc ion (in the fourth domain) catagorizing the protein as a metalloproteinase. The ion is organized tetrahedrally from a water molecule that can act as protinator for a leaving group after catalysis. A large groove (40 angstroms), which is located in close proximity to the zink ion, acts as the active site for substrate binding. The groove is a combination of side chains from domains two, three, and four. 

Project PagesEdit

  1. Patrick: Anthrax Toxin: Introduction 
  2. Patrick: Anthrax Toxin: Biological Function
  3. Patrick: Anthrax Toxin: Biosynthesis
  4. Patrick: Anthrax Toxin: Gene Sequence
  5. Patrick: Anthrax Toxin: Amino Acid Sequence and Composition
  6. Patrick: Anthrax Toxin: Secondary and Tertiary Structure
  7. Patrick: Anthrax Toxin: Domains and Structural Motifs
  8. Patrick: Anthrax Toxin: Interactions with macromolecules and small molecules
  9. Patrick: Anthrax Toxin: Molecular biodiversity and evolution
  10. Patrick: Anthrax Toxin: PyMOL Images
  11. Patrick: Anthrax Toxin: Literature Review
  12. Patrick: Anthrax Toxin: Useful online resources

References Edit

Anthrax Lethal Factor Domains and General Overview . Proteopedia.org

Pannifer AD et al. 2001. Crystal Structure of the Anthrax Lethal Factor .Nature. 414 (6860): 229-33. 

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