Novel Structural Features of Isoflavone Synthase from Medicago truncatula Shed Light on Its Unique Enzymatic Mechanism
10.13865/j.cnki.cjbmb.2025.05.1259
- VernacularTitle:蒺藜苜蓿异黄酮合成酶的新颖结构特征揭示其独特的酶促机制
- Author:
Chao SHI
1
;
Zhao-Yang YE
;
Fei XU
;
Xiang-Ning DU
;
Zhang-Xin CHEN
;
Ming-Yue GU
;
Jie DENG
;
Wei WANG
;
Liang-Yu LIU
;
Mei-Ying WANG
;
Xiao-Dong SU
;
He-Li LIU
;
Ming-Ying SHANG
;
Li-Xin HUANG
;
Zhen-Zhan CHANG
Author Information
1. 北京大学基础医学院生物物理系,北京 100191
- Publication Type:Journal Article
- Keywords:
cytochrome P450 enzyme(CYP450);
isoflavone synthase(IFS);
crystal structure;
ho-modimer
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(8):1204-1213,中插1-中插6
- CountryChina
- Language:Chinese
-
Abstract:
Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.
