8OFE

E.coli Peptide Deformylase with bound inhibitor

8OFE の概要

• エントリーDOI: 10.2210/pdb8ofe/pdb
• 分子名称: Peptide deformylase, (2R)-2-[[methanoyl(oxidanyl)amino]methyl]-N-[(2S)-3-methyl-1-oxidanylidene-1-[2-(sulfanylmethyl)pyrrolidin-1-yl]butan-2-yl]heptanamide, ZINC ION, ... (4 entities in total)
• 機能のキーワード: peptide deformylase (ec 3.5.1.88), inhibitor, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20019.62

構造登録者

Kirschner, H.,Stoll, R.,Hofmann, E. (登録日: 2023-03-15, 公開日: 2023-12-27, 最終更新日: 2024-04-10)

主引用文献

Kirschner, H.,John, M.,Zhou, T.,Bachmann, N.,Schultz, A.,Hofmann, E.,Bandow, J.E.,Scherkenbeck, J.,Metzler-Nolte, N.,Stoll, R.
Structural Insights into Antibacterial Payload Release from Gold Nanoparticles Bound to E. coli Peptide Deformylase.
Chemmedchem, 19:e202300538-e202300538, 2024

PubMed Abstract: The lack of new antibiotics and the rapidly rising number of pathogens resistant to antibiotics pose a serious problem to mankind. In bacteria, the cell membrane provides the first line of defence to antibiotics by preventing them from reaching their molecular target. To overcome this entrance barrier, it has been suggested that small Gold-Nanoparticles (AuNP) could possibly function as drug delivery systems for antibiotic ligands. Using actinonin-based ligands, we provide here proof-of-principle of AuNP functionalisation, the capability to bind and inhibit the target protein of the ligand, and the possibility to selectively release the antimicrobial payload. To this end, we successfully synthesised AuNP coated with thio-functionalised actinonin and a derivative. Interactions between N-enriched His-peptide deformylase 1-147 from E. coli (His-ecPDF 1-147) and compound-coated AuNP were investigated via 2D H-N-HSQC NMR spectra proving the direct binding to His-ecPDF 1-147. More importantly by adding dithiothreitol (DTT), we show that the derivative is successfully released from AuNPs while still bound to His-ecPDF 1-147. Our findings indicate that AuNP-conjugated ligands can address and bind intracellular target proteins. The system introduced here presents a new delivery platform for antibiotics and allows for the easy optimisation of ligand coated AuNPs.

PubMed: 38057137
DOI: 10.1002/cmdc.202300538

実験手法

X-RAY DIFFRACTION (1.4 Å)