Immunity proteins: enzyme inhibitors that avoid the active site

Immunity proteins are high affinity inhibitors of colicins – SOS-induced toxins released by bacteria during times of stress. Recent work has shown that nuclease-specific immunity proteins are exosite inhibitors, binding adjacent to the enzyme active site and inhibiting colicin activity indirectly. Unusually, their binding sites comprise a near contiguous sequence that lies N-terminal to active site sequences, raising the possibility that immunity proteins bind colicins co-translationally. Exosite binding accounts for the extensive sequence diversity seen at the interfaces of colicin–immunity protein complexes, which is not only a selective advantage to colicin-producing bacteria, but also represents a powerful model system for studying specificity in protein–protein recognition.