5FI5

HETEROYOHIMBINE SYNTHASE THAS1 FROM CATHARANTHUS ROSEUS - APO FORM

5FI5 の概要

• エントリーDOI: 10.2210/pdb5fi5/pdb
• 分子名称: Tetrahydroalstonine synthase, ZINC ION, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: heteroyohimbine synthase, medium chain dehydrogenase/reductase, nadp+ dependent enzyme, zinc binding site, oxidoreductase
• 由来する生物種: Catharanthus roseus (Madagascar periwinkle)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77215.53

構造登録者

Stavrinides, A.,Tatsis, E.C.,Caputi, L.,Foureau, E.,Stevenson, C.E.M.,Lawson, D.M.,Courdavault, V.,O'Connor, S.E. (登録日: 2015-12-22, 公開日: 2016-07-27, 最終更新日: 2024-01-10)

主引用文献

Stavrinides, A.,Tatsis, E.C.,Caputi, L.,Foureau, E.,Stevenson, C.E.,Lawson, D.M.,Courdavault, V.,O'Connor, S.E.
Structural investigation of heteroyohimbine alkaloid synthesis reveals active site elements that control stereoselectivity.
Nat Commun, 7:12116-12116, 2016

PubMed Abstract: Plants produce an enormous array of biologically active metabolites, often with stereochemical variations on the same molecular scaffold. These changes in stereochemistry dramatically impact biological activity. Notably, the stereoisomers of the heteroyohimbine alkaloids show diverse pharmacological activities. We reported a medium chain dehydrogenase/reductase (MDR) from Catharanthus roseus that catalyses formation of a heteroyohimbine isomer. Here we report the discovery of additional heteroyohimbine synthases (HYSs), one of which produces a mixture of diastereomers. The crystal structures for three HYSs have been solved, providing insight into the mechanism of reactivity and stereoselectivity, with mutation of one loop transforming product specificity. Localization and gene silencing experiments provide a basis for understanding the function of these enzymes in vivo. This work sets the stage to explore how MDRs evolved to generate structural and biological diversity in specialized plant metabolism and opens the possibility for metabolic engineering of new compounds based on this scaffold.

PubMed: 27418042
DOI: 10.1038/ncomms12116

実験手法

X-RAY DIFFRACTION (2.25 Å)