Identification of novel raloxifene adducts
in CYP3A4. (a) Magnum
identifies multiple 471 Da protein adducts in CYP3A4 after exposure
to raloxifene. Adducted residues are mapped to defined regions of
CYP3A4.50 (b) Observed 471 Da modifications
are shown on the structure of CYP3A4 as magenta spheres. Results were
identified by ≥3 PSMs, 1% FDR. Limelight view: https://limelight.yeastrc.org/limelight/go/0UjwIJNz45 (c) Extracted ion chromatograms (XICs) of 2+, 3+, and 4+ precursor
ions corresponding to CYP3A4 residue W126 elute as four distinct chromatographic
peaks likely representing regioisomers resulting from the different
positions43,48 in the raloxifene metabolite, diquinone
methide, that are subject to nucleophilic attack (inset structure,
red arrows). Unexposed control XICs show no signal (inset box, left).