YidC as a potential antibiotic target

Abstract

The membrane insertase YidC, is an essential bacterial component and functions in the folding and insertion of many membrane proteins during their biogenesis. It is a multispanning protein in the inner (cytoplasmic) membrane of Escherichia coli that binds its substrates in the "greasy slide" through hydrophobic interaction. The hydrophilic part of the substrate transiently localizes in the groove of YidC before it is translocated into the periplasm. The groove, which is flanked by the greasy slide, is within the center of the membrane, and provides a promising target for inhibitors that would block the insertase function of YidC. In addition, since the greasy slide is available for the binding of various substrates, it could also provide a binding site for inhibitory molecules. In this review we discuss in detail the structure and the mechanism of how YidC interacts not only with its substrates, but also with its partner proteins, the SecYEG translocase and the SRP signal recognition particle. Insight into the substrate binding to the YidC catalytic groove is presented. We wind up the review with the idea that the hydrophilic groove would be a potential site for drug binding and the feasibility of YidC-targeted drug development.

Keywords: Antibacterial target; Greasy slide; Hydrophilic groove; Membrane insertion; Membrane potential; YidC.