Calmodulin cleavage

The anthrax toxin is a tripartite toxin and consists ofthe binding component protective antigen (PA), the lethal factor (LF), which is a metalloprotease, and the edema factor (EF), which is a calmodulin-dependent adenylyl-cyclase. Both enzyme components are translocated via PA into target cells. PA is activated by furin-induced cleavage and forms heptamers, which are similar to the binding components of C2 toxin and iota toxin. In the low pH compartment of endosomes, the heptamers form pores to allow translocation of LF and EF. LF cleaves six of the seven MEKs (MAPK-kinases) thereby inhibiting these enzymes. The functional consequence is the blockade of the MAPK pathways that control cell proliferation, differentiation, inflammation, stress response, and survival. Whether this is the reason for the LT-induced cell death of macrophages is not clear [1]. 

Schepartz, A., and Cuenoud, B. (1990) Site-specific cleavage of the protein calmodulin using a trifluoperazine-based affinity reagent./. Am. Chem. Soc. 112, 3247-3249. 

Schematic illustration of the conversion of L-arginine to NO plus L-citrulline by the enzyme NO synthase. Conversion requires the presence of NADPH, calcium (Ca), calmodulin (CM), and O2. Calcium complexes with CM and the Ca-CM complex binds to the enzyme. The asterisk signifies the basic amino nitrogen atom that undergoes oxidation and cleavage to form NO. Both of the basic amino nittogens are equivalent and either nitrogen can be incorporated into NO.

GST, calmodulin-binding peptide, His-, FLAG-tag, protein A, glycoprotein D of HSV), or to enable its detection and/or selection, i.e. tags based on protein-reporters (/1-galactosidase, GFP, CAT, hGH) (Makrides, 1999). Tags can be fused to N- or C-terminal ends of the protein and a site for proteolytic cleavage is commonly included to eliminate the tag upon exploitation of its functionality. The proteases most commonly used are thrombin, enterokinase, factor Xa, and TEV (catalytic domain of Nia, the nuclear inclusion protein from tobacco etch virus). 

Calmodulin binding peolide Protein A domain TEV protease cleavage site... 

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