Insight into the antibacterial drug design and architectural mechanism of peptide recognition from the E. faecium peptide deformylase structure
- Insight into the antibacterial drug design and architectural mechanism of peptide recognition from the E. faecium peptide deformylase structure
- 남기현; 함정일; 아밋; 김은경; 정남현; 황광연
- antibacterial drug design; PDF complex with malonic acid; peptide deformylase; peptide recognition
- Issue Date
- VOL 74, NO 1, 261-265
- Following translation initiation, the formyl group of
the growing polypeptide is removed by peptide deformylase
(PDF) to yield the mature protein.1,2 PDF is
essential for bacterial growth, thus making it an attractive
target for the design of new antibiotic drugs.3,4 A
number of drugs targeting PDF have been developed;
however, some bacterial strains (including mutated resistant
strains) exhibit different levels of response to
these inhibitors in biological inhibition assays.5,6 Therefore,
additional design strategies for the development
of stronger and more specific PDF inhibitors are
Recent architectural studies of PDF provides a framework
for understanding the mechanism by which the
peptide interacts with the interior of the ribosomal tunnel.
7,8 Nonetheless, many questions remain to fully
understand the mechanism by which a new protein is
processed and targeted, as well as the co-and posttranslational
mechanisms required for the peptide to attain its
final folded state.
In this study, we report the detailed crystal structure
of the Enterococcus faecium PDF (EfPDF) complex with
malonic acid and demonstrate the architectural basis for
binding of the N-formyl polypeptide and for access of
inhibitors to the active site of the enzyme. These structural
studies will contribute to an improved understanding
of the basis of peptide recognition and, thus, for
antibacterial drug design.
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