Making allowances for anthrax

Crystal structure brings researchers closer to using anthrax to fight cancer.

Even the most imaginative spin doctors would struggle to put anthrax in a good light. However, US researchers have succeeded in putting a positive spin on the toxin by making an important step towards using it to help treat cancer.

The team from the Burnham Institute in La Jolla, California and the US National Institute of Allergy and Infectious Diseases (NIAID) has determined the crystal structure of the binding complex between anthrax toxin and one of its host receptors. Anthrax toxin comprises three proteins: protective antigen (PA), lethal factor (LF) and oedema factor (EF). The PA recognises a receptor on the surface of host cells and the receptor-bound protein then cleaves to enable EF and LF to form a pore structure which inserts in the cell membrane to transport the proteins into cells.

The US research team studied how PA binds to two anthrax receptors called TEM8 and CMG2 and determined the crystal structure of the PA-CMG2 binding complex. They suggest that the receptor acts as a pH-sensitive brace which controls when and where the pore inserts into the cell membrane. Robert Liddington, who led the team, expects the PA-TEM8 interactions to be very similar to those in the PA-CMG2 complex and plans to explore the crystal structure in silico.

Soluble versions of parts of CMG2 and TEM8 can protect against anthrax toxin by acting as decoys. Liddington told Chemistry World that his team is already developing peptide mimics of the receptor-binding surface of PA.

The anti-cancer hopes stem from the fact that the TEM8 receptor is mostly found on tumour blood vessel cells. One of the NIAID research team, Stephen Leppla, is currently developing the anthrax toxin as an anti-tumour agent.

Emma Davies