6jtd
Crystal structure of TcCGT1 in complex with UDPCrystal structure of TcCGT1 in complex with UDP
Structural highlights
Publication Abstract from PubMedIn this work, we explored the catalytic promiscuity of TcCGT1, a new C-glycosyltransferase (CGT) from the medicinal plant Trollius chinensis. TcCGT1 could efficiently and regio-specifically catalyze 8-C-glycosylation of 36 flavones and other flavonoids, and could also catalyze the O-glycosylation of diverse phenolics. Moreover, the crystal structure of TcCGT1 in complex with uridine diphosphate was determined at 1.85 A resolution. Structural analysis with molecular docking revealed a new model for catalytic mechanism of TcCGT1, which was initiated by substrate spontaneous deprotonation. The spacious binding pocket explains the robust substrate promiscuity, and binding pose of the substrate determines C- or O-glycosylation activity. Site-directed mutagenesis at two residues (I94E and G284K) switched C- to O-glycosylation. This work highlights TcCGT1 as the first plant CGT with a crystal structure and the first flavone 8-C-glycosyltransferase, and provides a basis for protein engineering to design efficient glycosylation biocatalysts for drug discovery. Molecular Characterization and Structural Basis of a Promiscuous C-Glycosyltransferase from Trollius chinensis.,He JB, Zhao P, Hu ZM, Liu S, Kuang Y, Zhang M, Li B, Yun CH, Qiao X, Ye M Angew Chem Int Ed Engl. 2019 Jun 4. doi: 10.1002/anie.201905505. PMID:31163097[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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