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Anthrax Lethal Factor02:59

Anthrax Lethal Factor

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Ribbon diagram of anthrax lethal factor with domains and general function labeled. Image courtesy of Andrew D. Pannifer, Thiang Yian Wong, Robert Schwarzenbacher, Martin Renatus, Carlo Petosa, Jadwiga Bienkowska, D. Borden Lacy, R. John Collier, Sukjoon Park, Stephen H. Leppla, Philip Hanna and Robert C. Liddington Nature 414, 229-233(8 November 2001) doi:10.1038/n35101998

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DomainsEdit

  1. This domain is responsible for the binding of lethal factor to protective antigen, one of the three anthrax proteins responsible for making the membrane channel on cell surfaces. Sitting atop the other three domains connected by a short turn, domain 1 consists of 12 short alpha-helices and four beta strands. 
  2. Domain two is responsible for the binding of  nicotinaminde adenine dinucleotide. It is labeled VIP2 since it shares structural similarities with its relative Bacillus Cereus's toxic catalytic domain VIP2. However, unlike VIP2, domain two of lethal factor lacks a critical glutamic acid and is suspected to not have ADP-ribosylating activity.  This domain which has six alpha-helices and five beta strands plays a role in substrate binding.
  3. With close association to domain four, domain three consists of highly specific substrate binding and hydrophobic residues. This domain is composed of six alpha-helices and no beta strands. It is part of the complex that forms a pocket where substrates bind. 
  4. This domain contains a zinc ion, nine alpha-helices and four beta strands. Along with domains two and three, it plays an integral role in substrate binding. It is labeled as the catalytic centre as it's primary function is to cleave MAPK substrates. 

Structural MotifsEdit

The most important structural motif of anthrax lethal factor is the binding grove located between domains three and four. This groove is easily seen on nearly any image of the folded protein and is the locaiton for MAPKK binding and cleavage.  Nonetheless, the structure of domains two, three, and four are crucial to the structure of the binding grove and consequently the lethality of the protein.

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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