Inhibition of the βbarrel assembly machine by a peptide that binds BamD
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https://doi.org/10.1073/pnas.1415955112Metadata
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Hagan, Christine L., Joseph S. Wzorek, and Daniel Kahne. 2015. “Inhibition of the ?-Barrel Assembly Machine by a Peptide That Binds BamD.” Proc Natl Acad Sci USA 112 (7) (February 2): 2011–2016. doi:10.1073/pnas.1415955112.Abstract
The protein complex that assembles integral membrane β-barrel proteins in the outer membranes of Gram-negative bacteria is an attractive target in the development of new antibiotics. This complex, the β-barrel assembly machine (Bam), contains two essential proteins, BamA and BamD. We have identified a peptide that inhibits the assembly of β-barrel proteins in vitro by characterizing the interaction of BamD with an unfolded substrate protein. This peptide is a fragment of the substrate protein and contains a conserved amino acid sequence. We have demonstrated that mutations of this sequence in the full-length substrate protein impair the protein’s assembly,implying that BamD’s interaction with this sequence is an important part of the assembly mechanism. Finally, we have found that in vivo expression of a peptide containing this sequence causes growth defects and sensitizes E. coli to antibiotics to which they are normally resistant. Therefore, inhibiting the binding of substrates to BamD is a viable strategy for developing new antibiotics directed against Gram-negative bacteria.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343090/Terms of Use
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