麦角新碱
组氨酸
化学
生物合成
半胱氨酸
立体化学
双加氧酶
活动站点
酶
硫黄
生物化学
有机化学
抗氧化剂
作者
Xinye Wang,HU Shi-sheng,Jun Wang,Tao Zhang,Ke Yao,Aiwen Wen,Guoliang Zhu,Arturo J. Vegas,Lixin Zhang,Yan Wang,Xueting Liu,Pinghua Liu
标识
DOI:10.1021/acscatal.3c04026
摘要
Ovothiol A and ergothioneine are thiol-histidine derivatives with sulfur substitutions at the δ-carbon or ε-carbon of the l-histidine imidazole ring, respectively. Both ovothiol A and ergothioneine have protective effects on many aging-related diseases, and the sulfur substitution plays a key role in determining their chemical and biological properties, while factors governing sulfur incorporation regioselectivities in ovothiol and ergothioneine biosynthesis in the corresponding enzymes (OvoA, Egt1, or EgtB) are not yet known. In this study, we have successfully obtained the first OvoA crystal structure, which provides critical information to explain their C-S bond formation regioselectivity. Furthermore, OvoATh2 exhibits several additional activities: (1) ergothioneine sulfoxide synthase activity akin to Egt1 in ergothioneine biosynthesis; (2) cysteine dioxygenase activity using l-cysteine and l-histidine analogues as substrates; (3) cysteine dioxygenase activity upon mutation of an active site tyrosine residue (Y406). The structural insights and diverse chemistries demonstrated by OvoATh2 pave the way for future comprehensive structure-function correlation studies.
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