PDF(Pubmed)
Abstract：
Selenoneine, an ergothioneine analog, is important for antioxidation and detoxification. SenB and SenA are two crucial enzymes that form carbon-selenium bonds in the selenoneine biosynthetic pathway. To investigate their underlying catalytic mechanisms, we obtained complex structures of SenB with its substrate UDP-N-acetylglucosamine (UDP-GlcNAc) and SenA with N-α-trimethyl histidine (TMH). SenB adopts a type-B glycosyltransferase fold. Structural and functional analysis of the interaction network at the active center provide key information on substrate recognition and suggest a metal-ion-independent, inverting mechanism is utilized for SenB-mediated selenoglycoside formation. Moreover, the complex structure of SenA with TMH and enzymatic activity assays highlight vital residues that control substrate binding and specificity. Based on the conserved structure and substrate-binding pocket of the type I sulfoxide synthase EgtB in the ergothioneine biosynthetic pathway, a similar reaction mechanism was proposed for the formation of C-Se bonds by SenA. The structures provide knowledge on selenoneine synthesis and lay groundwork for further applications of this pathway.
摘要：
硒酮,麦角硫因类似物，对抗氧化和解毒很重要。SenB和SenA是硒酮生物合成途径中形成碳-硒键的两种关键酶。为了研究它们潜在的催化机理，我们获得了SenB与其底物UDP-N-乙酰葡糖胺（UDP-GlcNAc）和SenA与N-α-三甲基组氨酸（TMH）的复杂结构。SenB采用B型糖基转移酶折叠。活性中心的相互作用网络的结构和功能分析提供了有关底物识别的关键信息，并提出了与金属离子无关的方法，反转机制用于SenB介导的硒糖苷形成。此外，SenA与TMH的复杂结构和酶活性测定突出了控制底物结合和特异性的重要残基。基于麦角硫因生物合成途径中I型亚砜合酶EgtB的保守结构和底物结合袋，SenA对C-Se键的形成提出了类似的反应机理。这些结构提供了硒酮合成的知识，并为该途径的进一步应用奠定了基础。
