Keywords: cannabinoid biosynthesis; cannabinoid synthase; berberine bridge enzyme; cannabielsoin; cannabigerolic acid; Pichia pastoris
ReadSLC25A47 was initially identified as a mitochondrial HCC-downregulated carrier protein, but its physiological functions and transport substrates are unknown. We aimed to investigate the physiological role of SLC25A47 in hepatic metabolism.
ReadMouse monoclonal antibody M4M was recently designed to block human TRPM4 channel. The polypeptide for generating M4M is composed of peptide A1 between the transmembrane segment 5 (S5) and the pore, and a second peptide A2 between the pore and the transmembrane segment 6 (S6).
ReadSynthetic biology efforts for cannabinoid research have seen a rapid expansion in recent years. This is in response to the increasing awareness and legalization of the secondary metabolites from Cannabis sativa, dubbed the green rush.
ReadSolute carrier transporters are the second largest family of membrane proteins responsible for the transport of various substances such as saccharides, lipids, amino acids, and inorganic ions across cellular membranes (Zhang et al., 2019). One third of all solute carriers such as SLC2, SLC22, and SLC45 subfamily belong to the major facilitator superfamily clan (Chen et al., 2014; Perland et al., 2017).
ReadKEYWORDS: cannabinoid biosynthesis, computational protein engineering, synthetic biology, enzyme design, prenyltransferase
ReadSignificance Statement In this study, we reported for the first time the covalent MBI of CYP3A by PEM and deciphered its bioactivation pathway involving the metabolic activation of PEM and its major O-desmethylated metabolite to reactive iminium ion intermediates. Following which, a unique covalent docking methodology was harnessed to unravel the structural and molecular determinants underpinning its inactivation. Findings from our study lay the foundation for future investigation of clinically-relevant drug-drug interactions between PEM and concomitant substrates of CYP3A.
ReadIn this study, we reported for the first time the covalent MBI of CYP3A by PEM and deciphered its bioactivation pathway involving the metabolic activation of PEM and its major O-desmethylated metabolite to reactive iminium ion intermediates. Following which, a unique covalent docking methodology was harnessed to unravel the structural and molecular determinants underpinning its inactivation. Findings from our study lay the foundation for future investigation of clinically-relevant drug-drug interactions between PEM and concomitant substrates of CYP3A.
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