8RHR

E.coli Peptide Deformylase with bound inhibitor BB4

8RHR の概要

• エントリーDOI: 10.2210/pdb8rhr/pdb
• 分子名称: Peptide deformylase, ZINC ION, 2-(5-bromo-1H-indol-3-yl)-N-hydroxyacetamide, ... (6 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: 20135.51

構造登録者

Kirschner, H.,Stoll, R.,Hofmann, E. (登録日: 2023-12-16, 公開日: 2024-04-17, 最終更新日: 2024-05-08)

主引用文献

Kirschner, H.,Heister, N.,Zouatom, M.,Zhou, T.,Hofmann, E.,Scherkenbeck, J.,Stoll, R.
Toward More Selective Antibiotic Inhibitors: A Structural View of the Complexed Binding Pocket of E. coli Peptide Deformylase.
J.Med.Chem., 67:6384-6396, 2024

PubMed Abstract: Peptide deformylase (PDF) is involved in bacterial protein maturation processes. Originating from the interest in a new antibiotic, tremendous effort was put into the refinement of PDF inhibitors (PDFIs) and their selectivity. We obtained a full NMR backbone assignment the emergent additional protein backbone resonances of ecPDF 1-147 in complex with 2-(5-bromo-1-indol-3-yl)--hydroxyacetamide (), a potential new structural scaffold for more selective PDFIs. We also determined the complex crystal structures of PDF (ecPDF fl) and . Our structure suggests an alternative ligand conformation within the protein, a possible starting point for further selectivity optimization. The orientation of the second ligand conformation in the crystal structure points toward a small region of the S1' pocket, which differs between bacterial PDFs and human PDF. Moreover, we analyzed the binding mode of via NMR TITAN line shape analysis, revealing an induced fit mechanism.

PubMed: 38574272
DOI: 10.1021/acs.jmedchem.3c02382

実験手法

X-RAY DIFFRACTION (1.42 Å)