Structure Report for: 8EA2

Pan, H., Wang, X.

Title: The protein conformational basis of isoflavone biosynthesis
Wang X, Pan H, Sagurthi S, Paris V, Zhuo C, Dixon RA
Ref: Commun Biol, 5:1249, 2022 : PubMed
Abstract


ESTHER: Wang_2022_Commun.Biol_5_1249
PubMedSearch: Wang 2022 Commun.Biol 5 1249
PubMedID: 36376429
Gene_locus related to this paper: pueml-e9m5g1

Abstract

Isoflavonoids play important roles in plant defense and also exhibit a range of mammalian health-promoting activities. Their biosynthesis is initiated by two enzymes with unusual catalytic activities; 2-hydroxyisoflavanone synthase (2-HIS), a membrane-bound cytochrome P450 catalyzing a coupled aryl-ring migration and hydroxylation, and 2-hydroxyisoflavanone dehydratase (2-HID), a member of a large carboxylesterase family that paradoxically catalyzes dehydration of 2-hydroxyisoflavanones to isoflavone. Here we report the crystal structures of 2-HIS from Medicago truncatula and 2-HID from Pueraria lobata. The 2-HIS structure reveals a unique cytochrome P450 conformation and heme and substrate binding mode that facilitate the coupled aryl-ring migration and hydroxylation reactions. The 2-HID structure reveals the active site architecture and putative catalytic residues for the dual dehydratase and carboxylesterase activities. Mutagenesis studies revealed key residues involved in substrate binding and specificity. Understanding the structural basis of isoflavone biosynthesis will facilitate the engineering of new bioactive isoflavonoids.