Insight into the antibacterial drug design and architectural mechanism of peptide recognition from the E. faecium peptide deformylase structure

Title
Insight into the antibacterial drug design and architectural mechanism of peptide recognition from the E. faecium peptide deformylase structure
Authors
남기현함정일아밋김은경정남현황광연
Keywords
antibacterial drug design; PDF complex with malonic acid; peptide deformylase; peptide recognition
Issue Date
2009-01
Publisher
Proteins
Citation
VOL 74, NO 1, 261-265
Abstract
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 warranted. 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.
URI
http://pubs.kist.re.kr/handle/201004/34804
ISSN
0887-3585
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE