8T87

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

Summary for 8T87

• Entry DOI: 10.2210/pdb8t87/pdb
• Descriptor: Fluorophosphonate-binding serine hydrolase E, MAGNESIUM ION (3 entities in total)
• Functional Keywords: fphe, staphylococcus aureus, s. aureus, fluorophosphonate-binding, serine hydrolases, lipase, hydrolase
• Biological source: Staphylococcus aureus USA300-0114
• Total number of polymer chains: 2
• Total formula weight: 62696.03

Authors

Fellner, M. (deposition date: 2023-06-22, release date: 2024-03-06, Last modification date: 2024-03-27)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.62 Å)