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

IF 3.5 4区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Kai Rogge, Tobias Johannes Wagner, Dirk Hoffmeister, Bernhard Rupp, Sebastiaan Werten
{"title":"Substrate recognition by the 4-hydroxytryptamine kinase PsiK in psilocybin biosynthesis.","authors":"Kai Rogge, Tobias Johannes Wagner, Dirk Hoffmeister, Bernhard Rupp, Sebastiaan Werten","doi":"10.1002/1873-3468.15042","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FEBS Letters","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/1873-3468.15042","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0

Abstract

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.

迷幻药生物合成过程中 4-羟色胺激酶 PsiK 的底物识别。
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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
FEBS Letters
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信