迷幻药生物合成过程中 4-羟色胺激酶 PsiK 的底物识别。

IF 3.5 4区生物学 Q1 Biochemistry, Genetics and Molecular Biology

FEBS Letters Pub Date : 2024-10-24 DOI:10.1002/1873-3468.15042

Kai Rogge, Tobias Johannes Wagner, Dirk Hoffmeister, Bernhard Rupp, Sebastiaan Werten

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引用次数: 0

摘要

迷幻蘑菇中的天然致幻剂--迷幻蘑菇素是一种非常有前途的候选药物，可用于治疗抑郁症和其他几种精神疾病。从氨基酸 l-色氨酸中生物合成迷幻蘑菇素涉及四种严格按顺序进行的修饰。其中第三种是由 PsiK 催化的依赖 ATP 的 4-hydroxytryptamine 中间体磷酸化。在此，我们对这种激酶进行了晶体学分析和基于结构的诱变研究，从而深入了解了它识别底物的模式。我们的工作成果将为未来旨在产生具有更强治疗特性的迷幻药变体的生物工程工作提供支持。

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Substrate recognition by the 4-hydroxytryptamine kinase PsiK in psilocybin biosynthesis.

Psilocybin, the natural hallucinogen from Psilocybe (magic) mushrooms, is a highly promising drug candidate for the treatment of depression and several other mental health conditions. Biosynthesis of psilocybin from the amino acid l-tryptophan involves four strictly sequential modifications. The third of these, ATP-dependent phosphorylation of the intermediate 4-hydroxytryptamine, is catalysed by PsiK. Here we present a crystallographic analysis and a structure-based mutagenesis study of this kinase, providing insight into its mode of substrate recognition. The results of our work will support future bioengineering efforts aimed at generating variants of psilocybin with enhanced therapeutic properties.

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来源期刊

FEBS Letters 生物-生化与分子生物学

CiteScore

7.00

自引率

2.90%

发文量

303

审稿时长

1.0 months

期刊介绍： FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.