Sec, drugs and rock’n’roll: antibiotic targeting of bacterial protein translocation

Abstract

A large number of bacterial proteins are active in extracytoplasmic locations. Targeting and membrane translocation of the vast majority of these secretory and membrane polypeptides is mediated by the Sec pathway. Protein secretion requires the co-ordinated and sequential action of targeting factors on the cis-side of the membrane, a complex membrane-embedded protein translocase and maturation enzymes on the trans-side. Recently, significant advances in the molecular genetics and biochemistry of the Sec pathway have revealed that several of the Sec pathway components are essential for bacterial viability and/or pathogenicity. Moreover, several biochemical assays and structural insights have become available. Importantly, some of the Sec components are unique to bacteria. These developments raise the possibility that the bacterial protein translocase and other Sec pathway components could become formidable targets for antibacterial drug discovery.