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8hok

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crystal structure of UGT71AP2

Structural highlights

8hok is a 1 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 2.15Å
Ligands:	,
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 hydrogenâdeuterium 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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wang Z, Du X, Ye G, Wang H, Liu Y, Liu C, Li F, Ågren H, Zhou Y, Li J, He C, Guo DA, Ye M. Functional characterization, structural basis, and protein engineering of a rare flavonoid 2'-O-glycosyltransferase from Scutellaria baicalensis. Acta Pharm Sin B. 2024 Aug;14(8):3746-3759. PMID:39220864 doi:10.1016/j.apsb.2024.04.001