8PU5

Crystal structure of the Acyl-CoA dehydrogenase FadE1(PA0506) E441A from Pseudomonas aeruginosa complexed with C16CoA

8PU5 の概要

• エントリーDOI: 10.2210/pdb8pu5/pdb
• 分子名称: Probable acyl-CoA dehydrogenase, Palmitoyl-CoA, 1,2-ETHANEDIOL, ... (7 entities in total)
• 機能のキーワード: acyl-coa dehydrogenase, beta-oxidation, oxidoreductase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 67218.20

構造登録者

Wang, M.,Brear, P.,Welch, M. (登録日: 2023-07-16, 公開日: 2025-02-12, 最終更新日: 2025-05-21)

主引用文献

Wang, M.,Medarametla, P.,Kronenberger, T.,Deingruber, T.,Brear, P.,Figueroa, W.,Ho, P.M.,Krueger, T.,Pearce, J.C.,Poso, A.,Wakefield, J.G.,Spring, D.R.,Welch, M.
Pseudomonas aeruginosa acyl-CoA dehydrogenases and structure-guided inversion of their substrate specificity.
Nat Commun, 16:2334-2334, 2025

PubMed Abstract: Fatty acids are a primary source of carbon for Pseudomonas aeruginosa (PA) in the airways of people with cystic fibrosis (CF). Here, we use tandem mass-tag proteomics to analyse the protein expression profile of a CF clinical isolate grown on different fatty acids. Two fatty acyl-CoA dehydrogenases (designated FadE1 and FadE2) are strongly induced during growth on fatty acids. FadE1 displays a strong preference for long-chain acyl-CoAs, whereas FadE2 exclusively utilizes medium-chain acyl-CoAs. Structural analysis of the enzymes enables us to identify residues comprising the substrate selectivity filter in each. Engineering these residues enables us to invert the substrate specificity of each enzyme. Mutants in fadE1 displayed impaired virulence in an infection model, and decreased growth on long chain fatty acids. The unique features of the substrate binding pocket enable us to identify an inhibitor that is differentially active against FadE1 and FadE2.

PubMed: 40057486
DOI: 10.1038/s41467-025-57532-z

実験手法

X-RAY DIFFRACTION (1.44 Å)