Fig 1. Examples of cofactor regulation of secreted bacterial enzymes.

Toxins delivered to their target cell by either direct injection (yellow) or cell surface binding and translocation (green) can be host cofactor activated. These enzymes generally contain dynamic structures that assume a catalytically active fold upon complex formation with a host factor. The key depicts this process through cofactor-mediated organization (blue) of an unstructured sequence. Apo, the apoenzyme catalytically-inactive state. Holo, the holoenzyme active state in which the toxin is in complex with its cofactor. CyaA, the plasma membrane-localized nucleotide cyclase toxin from Bordetella pertussis complexed to calcium ions and calmodulin. EF, edema factor from Bacillus anthracis, binds to calmodulin in a different orientation than CyaA. PA, protective antigen. The cofactor for cholera toxin (ARF) is shown in the myristolated, GTP-bound form. ER, endoplasmic reticulum, with cholera toxin peptide being secreted through ER protein channels.