8T88

FphE, Staphylococcus aureus fluorophosphonate-binding serine hydrolases E, Oxadiazolone JJ004 bound

8T88 の概要

• エントリーDOI: 10.2210/pdb8t88/pdb
• 分子名称: Fluorophosphonate-binding serine hydrolase E, methyl 2-formyl-2-[4-(undec-10-ynamido)phenyl]hydrazine-1-carboxylate, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: fphe, staphylococcus aureus, s. aureus, fluorophosphonate-binding, serine hydrolases, lipase, hydrolase
• 由来する生物種: Staphylococcus aureus USA300-0114
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63345.70

構造登録者

Fellner, M. (登録日: 2023-06-22, 公開日: 2024-03-06, 最終更新日: 2024-11-13)

主引用文献

Jo, J.,Upadhyay, T.,Woods, E.C.,Park, K.W.,Pedowitz, N.J.,Jaworek-Korjakowska, J.,Wang, S.,Valdez, T.A.,Fellner, M.,Bogyo, M.
Development of Oxadiazolone Activity-Based Probes Targeting FphE for Specific Detection of Staphylococcus aureus Infections.
J.Am.Chem.Soc., 146:6880-6892, 2024

PubMed Abstract: () is a major human pathogen that is responsible for a wide range of systemic infections. Since its propensity to form biofilms poses formidable challenges for both detection and treatment, tools that can be used to specifically image biofilms are highly valuable for clinical management. Here, we describe the development of oxadiazolone-based activity-based probes to target the -specific serine hydrolase FphE. Because this enzyme lacks homologues in other bacteria, it is an ideal target for selective imaging of infections. Using X-ray crystallography, direct cell labeling, and mouse models of infection, we demonstrate that oxadiazolone-based probes enable specific labeling of bacteria through the direct covalent modification of the FphE active site serine. These results demonstrate the utility of the oxadizolone electrophile for activity-based probes and validate FphE as a target for the development of imaging contrast agents for the rapid detection of infections.

PubMed: 38411555
DOI: 10.1021/jacs.3c13974

実験手法

X-RAY DIFFRACTION (1.54 Å)