松素生物合成中的第二次甲基化是由延伸到围绕甲基转移酶活性部位的二次球体内的结网络启用的
Jesse Hudspeth1, Kai Rogge2,3, Tobias Wagner2
1Department of Chemistry, Colorado School of Mines, 1500 Illinois Street, Golden, CO, 80401, USA.
Chembiochem : a European journal of chemical biology
|October 16, 2024
概括
这种Psilocybe cubensis的甲基转移酶是PsiM.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 结构生物学 结构生物学
背景情况:
- Psilocybe cubensis PsiM是一种依赖SAM的甲基转移酶,催化了psilocybin生物合成的最后一步.
- PsiM很可能是从单甲基化RNA甲基转移酶进化而来的,并获得了一个关键的M247N替代二甲基化.
- Asn247对于PsiM的二甲基化能力至关重要.
研究的目的:
- 调查Asn247在PsiM的单甲基和二甲基化中的作用.
- 用改变的Asn247.7来描述PsiM变体的动力和结构特性.
主要方法:
- 位点定向的突变发生产生PsiM变体 (PsiMN247M,PsiMN247A).
- 野生类型和变种酶的动态分析.
- 用X射线晶体学来确定三元复合体的结构.
主要成果:
- PsiM变体显示了基质结合 (20倍) 和催化效率 (2倍) 的降低.
- 晶体结构揭示了非生产性构造和变体中不规则的基质结合.
- 观察到β5-β7板的不稳定,以及罗斯曼折叠中保留的β转折.
结论:
- 通过提供活性位点空间,Asn247对于容纳多重甲基化是必不可少的.
- Asn247参与了稳定关键二次结构的键网络.
- 这些稳定性相互作用对于由PsiM进行的norbaeocystin最佳甲基化至关重要.
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