Structural highlights
Function
[DEF_STRA3] Removes the formyl group from the N-terminal Met of newly synthesized proteins. Requires at least a dipeptide for an efficient rate of reaction. N-terminal L-methionine is a prerequisite for activity but the enzyme has broad specificity at other positions.
Publication Abstract from PubMed
Peptide deformylase (PDF) is considered an excellent target to develop antibiotics. We have performed an extensive characterization of a new PDF from the pathogen Streptococcus agalactiae, showing properties similar to other known PDFs. S. agalactiae PDF could be used as PDF prototype as it allowed to get complete sets of 3-dimensional, biophysical and kinetic data with virtually any inhibitor compound. Structure-activity relationship analysis with this single reference system allowed us to reveal distinct binding modes for different PDF inhibitors and the key role of a hydrogen bond in potentiating the interaction between ligand and target. We propose this protein as an irreplaceable tool, allowing easy and relevant fine comparisons between series, to design, challenge and validate novel series of inhibitors. As proof-of-concept, we report here the design and synthesis of effective specific bacterial PDF inhibitors of an oxadiazole series with potent antimicrobial activity against a multidrug resistant clinical isolate.
A unique peptide deformylase platform to rationally design and challenge novel active compounds.,Fieulaine S, Alves de Sousa R, Maigre L, Hamiche K, Alimi M, Bolla JM, Taleb A, Denis A, Pages JM, Artaud I, Meinnel T, Giglione C Sci Rep. 2016 Oct 20;6:35429. doi: 10.1038/srep35429. PMID:27762275[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fieulaine S, Alves de Sousa R, Maigre L, Hamiche K, Alimi M, Bolla JM, Taleb A, Denis A, Pages JM, Artaud I, Meinnel T, Giglione C. A unique peptide deformylase platform to rationally design and challenge novel active compounds. Sci Rep. 2016 Oct 20;6:35429. doi: 10.1038/srep35429. PMID:27762275 doi:http://dx.doi.org/10.1038/srep35429
