5JEY

Crystal structure of type 2 PDF from Streptococcus agalactiae, crystallized in cacodylate buffer

Summary for 5JEY

• Entry DOI: 10.2210/pdb5jey/pdb
• Descriptor: Peptide deformylase, NICKEL (II) ION (3 entities in total)
• Functional Keywords: pdf, type 2, nme, n-terminal methionine excision, streptococcus agalactiae, inhibitor, hydrolase
• Biological source: Streptococcus agalactiae
• Total number of polymer chains: 1
• Total formula weight: 23363.84

Authors

Fieulaine, S.,Giglione, C.,Meinnel, T. (deposition date: 2016-04-19, release date: 2016-11-30, Last modification date: 2024-01-10)

Primary citation

Fieulaine, S.,Alves de Sousa, R.,Maigre, L.,Hamiche, K.,Alimi, M.,Bolla, J.M.,Taleb, A.,Denis, A.,Pages, J.M.,Artaud, I.,Meinnel, T.,Giglione, C.
A unique peptide deformylase platform to rationally design and challenge novel active compounds.
Sci Rep, 6:35429-35429, 2016

PubMed Abstract: 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.

PubMed: 27762275
DOI: 10.1038/srep35429

Experimental method

X-RAY DIFFRACTION (2.8 Å)