8UIX

FphE, Staphylococcus aureus fluorophosphonate-binding serine hydrolases E, boronic acid-based compound Y43 bound

8UIX の概要

• エントリーDOI: 10.2210/pdb8uix/pdb
• 分子名称: Fluorophosphonate-binding serine hydrolase E, (3,5-dimethoxyphenyl)boronic acid (3 entities in total)
• 機能のキーワード: fphe, staphylococcus aureus, s. aureus, fluorophosphonate-binding, serine hydrolases, lipase, boronic acid, covalent, boron-serine, boron-histidine, hydrolase
• 由来する生物種: Staphylococcus aureus subsp. aureus USA300
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62914.16

構造登録者

Fellner, M. (登録日: 2023-10-10, 公開日: 2024-10-23, 最終更新日: 2025-06-25)

主引用文献

Upadhyay, T.,Woods, E.C.,Dela Ahator, S.,Julin, K.,Faucher, F.F.,Uddin, M.J.,Hollander, M.J.,Pedowitz, N.J.,Abegg, D.,Hammond, I.,Eke, I.E.,Wang, S.,Chen, S.,Bennett, J.M.,Jo, J.,Lentz, C.S.,Adibekian, A.,Fellner, M.,Bogyo, M.
Identification of covalent inhibitors of Staphylococcus aureus serine hydrolases important for virulence and biofilm formation.
Nat Commun, 16:5046-5046, 2025

PubMed Abstract: Staphylococcus aureus is a leading cause of bacteria-associated mortality worldwide. New tools are needed to both image and treat this pathogen. We previously identified a group of S. aureus serine hydrolases (Fphs), which regulate aspects of virulence and lipid metabolism. However, due to high structural and functional similarities, it remains challenging to distinguish the specific roles of members of this family. Here, we apply a high-throughput screening approach using a library of covalent electrophiles to identify inhibitors for FphB, FphE, and FphH. We identify selective covalent inhibitors for each target without the need for extensive medicinal chemistry optimization. Structural and biochemical analysis identify novel binding modes for several of the inhibitors. Functional studies using the inhibitors suggest that all three hydrolases likely play distinct functional roles in biofilm formation and virulence. This approach has the potential to be applied to target hydrolases in other diverse pathogens or higher eukaryotes.

PubMed: 40447595
DOI: 10.1038/s41467-025-60367-3

実験手法

X-RAY DIFFRACTION (2.39 Å)