8hoj | pdb_00008hoj

Crystal structure of UGT71AP2 in complex with UDP

spinqualitylabelsall models 8hoj, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8hoj is a 2 chain structure with sequence from Scutellaria baicalensis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.9Å Ligands: UDP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Glycosylation is an important post-modification reaction in plant secondary metabolism, and contributes to structural diversity of bioactive natural products. In plants, glycosylation is usually catalyzed by UDP-glycosyltransferases. Flavonoid 2'-O-glycosides are rare glycosides. However, no UGTs have been reported, thus far, to specifically catalyze 2'-O-glycosylation of flavonoids. In this work, UGT71AP2 was identified from the medicinal plant Scutellaria baicalensis as the first flavonoid 2'-O-glycosyltransferase. It could preferentially transfer a glycosyl moiety to 2'-hydroxy of at least nine flavonoids to yield six new compounds. Some of the 2'-O-glycosides showed noticeable inhibitory activities against cyclooxygenase 2. The crystal structure of UGT71AP2 (2.15 A) was solved, and mechanisms of its regio-selectivity was interpreted by pK (a) calculations, molecular docking, MD simulation, MM/GBSA binding free energy, QM/MM, and hydrogen‒deuterium exchange mass spectrometry analysis. Through structure-guided rational design, we obtained the L138T/V179D/M180T mutant with remarkably enhanced regio-selectivity (the ratio of 7-O-glycosylation byproducts decreased from 48% to 4%) and catalytic efficiency of 2'-O-glycosylation (k (cat)/K (m), 0.23 L/(s.mumol), 12-fold higher than the native). Moreover, UGT71AP2 also possesses moderate UDP-dependent de-glycosylation activity, and is a dual function glycosyltransferase. This work provides an efficient biocatalyst and sets a good example for protein engineering to optimize enzyme catalytic features through rational design. Functional characterization, structural basis, and protein engineering of a rare flavonoid 2'-O-glycosyltransferase from Scutellaria baicalensis.,Wang Z, Du X, Ye G, Wang H, Liu Y, Liu C, Li F, Agren H, Zhou Y, Li J, He C, Guo DA, Ye M Acta Pharm Sin B. 2024 Aug;14(8):3746-3759. doi: 10.1016/j.apsb.2024.04.001. Epub , 2024 Apr 5. PMID:39220864 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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