Pyridoxal phosphate-dependent enzymes (PLP-DEs) are ubiquitous, catalytically diverse and essential for basic metabolism. A chemical proteomic strategy was developed for reporting on PLP-DEs in cells using functionalized PL-cofactor mimics. Biochemical, crystallographic and quantitative MS studies show that the probes are effectively absorbed, metabolized and integrated into biological systems. Our method enabled access to 73% of the Staphylococcus aureus PLP-ome and could be used to identify new PLP-DEs, screen for drug off-targets and probe enzyme active sites.
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Pyridoxal phosphate-dependent enzymes (PLP-DEs) are ubiquitous, catalytically diverse and essential for basic metabolism. A chemical proteomic strategy was developed for reporting on PLP-DEs in cells using functionalized PL-cofactor mimics. Biochemical, crystallographic and quantitative MS studies show that the probes are effectively absorbed, metabolized and integrated into biological systems. Our method enabled access to 73% of the Staphylococcus aureus PLP-ome and could be used to identify ne...
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