8SBQ

FphE, Staphylococcus aureus fluorophosphonate-binding serine hydrolases E, fluorophosphonate JB101 bound, dimer crystal form 1

8SBQ の概要

• エントリーDOI: 10.2210/pdb8sbq/pdb
• 分子名称: Fluorophosphonate-binding serine hydrolases E, ethyl (R)-(10-{[(but-3-yn-1-yl)carbamoyl]oxy}decyl)phosphonofluoridate, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: fphe, staphylococcus aureus fluorophosphonate-binding serine hydrolases e, fluorophosphonate jb101 bound, 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: 63349.92

構造登録者

Fellner, M. (登録日: 2023-04-04, 公開日: 2024-04-17, 最終更新日: 2026-04-01)

主引用文献

Jo, J.,Upadhyay, T.,You, X.,Bennett, J.M.,Lee, H.,Bogyo, M.,Fellner, M.
Unique structural and ligand-binding properties of the Staphylococcus aureus serine hydrolase FphE.
Proc.Natl.Acad.Sci.USA, 123:e2532683123-e2532683123, 2026

PubMed Abstract: is a human pathogen capable of forming biofilms that complicate treatment and facilitate chronic infections. A family of serine hydrolases are important regulators of virulence and biofilm formation. Among these, FphE is highly specific to and therefore a viable target for both imaging and therapy. Here, we present bioinformatic and structural evidence that FphE may be involved in aromatic compound metabolism. In addition, 12 distinct crystal forms reveal that FphE exists as a highly unusual but stable and flexible, cross-subunit homodimer, unique to the large alpha/beta hydrolase superfamily. Substrate engagement favors retention of the dimeric state, which is a more catalytically active form of the enzyme, and small-angle X-ray scattering confirms that the dimeric architecture occurs in solution. High-resolution cocrystal structures of FphE covalently bound to two chemically distinct ligands reveal different modes of active site engagement, supporting an atypical structural plasticity of the dimer interface. Together, these findings establish FphE as a structurally unique alpha/beta hydrolase and provide a foundation for structure-guided development of -specific inhibitors and imaging probes.

PubMed: 41875159
DOI: 10.1073/pnas.2532683123

実験手法

X-RAY DIFFRACTION (1.5 Å)