arachidonoylserotonin and pyridine

Cytochrome P450 2U1 (CYP2U1) has been identified from the human genome and is highly conserved in the living kingdom. It is considered as an "orphan" protein as few data are available on its physiological function(s) and spectral characteristics. Its only known substrates reported so far are unsaturated fatty acids such as arachidonic acid (AA), and, more recently, N-arachidonoylserotonin (AS) and some xenobiotics related to debrisoquine (Deb) and terfenadine.. We have expressed CYP2U1 in E. coli and performed UV-vis and EPR spectroscopy experiments with purified CYP2U1 alone and in the presence of substrates and imidazole and pyridine derivatives. Docking experiments using a 3D homology model of CYP2U1 were done to explain the observed spectroscopic data and the different regioselectivities of the oxidations of AA and AS.. The UV-vis and EPR spectra of native recombinant human CYP2U1 revealed a predominant low-spin hexacoordinate Fe. Our study describes for the first time the mode of interaction of several Fe

Topics: Arachidonic Acid; Arachidonic Acids; Biocatalysis; Cytochrome P450 Family 2; Debrisoquin; Electron Spin Resonance Spectroscopy; Escherichia coli; Humans; Imidazoles; Lauric Acids; Ligands; Models, Molecular; Molecular Docking Simulation; Oxidation-Reduction; Protein Binding; Pyridines; Recombinant Proteins; Serotonin; Spectrophotometry, Ultraviolet; Substrate Specificity