Immunity proteins: enzyme inhibitors that avoid the active site

Immunity proteins are high affinity inhibitors of colicins-SOS-induced toxi ns released by bacteria during times of stress. Recent work has shown that nuclease-specific immunity proteins are exosite inhibitors, binding adjacen t to the enzyme active site and inhibiting colicin activity indirectly. Unu sually, their binding sites comprise a near contiguous sequence that lies N -terminal to active site sequences, raising the possibility that immunity p roteins bind colicins co-translation ally. Exosite binding accounts for the extensive sequence diversity seen at the interfaces of colicin-immunity pr otein complexes, which is not only a selective advantage to colicin-produci ng bacteria, but also represents a powerful model system for studying speci ficity in protein-protein recognition.