5FEU

Noroxomaritidine/Norcraugsodine Reductase in complex with NADP+

5FEU の概要

• エントリーDOI: 10.2210/pdb5feu/pdb
• 関連するPDBエントリー: 5FF9 5FFF
• 分子名称: Noroxomaritidine/Norcraugsodine Reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• 機能のキーワード: short-chain dehydrogenase/reductase alkaloid biosynthesis, oxidoreductase
• 由来する生物種: Narcissus pseudonarcissus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31930.65

構造登録者

Holland, C.,Jez, J.M. (登録日: 2015-12-17, 公開日: 2016-06-08, 最終更新日: 2023-09-27)

主引用文献

Kilgore, M.B.,Holland, C.K.,Jez, J.M.,Kutchan, T.M.
Identification of a Noroxomaritidine Reductase with Amaryllidaceae Alkaloid Biosynthesis Related Activities.
J.Biol.Chem., 291:16740-16752, 2016

PubMed Abstract: Amaryllidaceae alkaloids are a large group of plant natural products with over 300 documented structures and diverse biological activities. Several groups of Amaryllidaceae alkaloids including the hemanthamine- and crinine-type alkaloids show promise as anticancer agents. Two reduction reactions are required for the production of these compounds: the reduction of norcraugsodine to norbelladine and the reduction of noroxomaritidine to normaritidine, with the enantiomer of noroxomaritidine dictating whether the derivatives will be the crinine-type or hemanthamine-type. It is also possible for the carbon-carbon double bond of noroxomaritidine to be reduced, forming the precursor for maritinamine or elwesine depending on the enantiomer reduced to an oxomaritinamine product. In this study, a short chain alcohol dehydrogenase/reductase that co-expresses with the previously discovered norbelladine 4'-O-methyltransferase from Narcissus sp. and Galanthus spp. was cloned and expressed in Escherichia coli Biochemical analyses and x-ray crystallography indicates that this protein functions as a noroxomaritidine reductase that forms oxomaritinamine from noroxomaritidine through a carbon-carbon double bond reduction. The enzyme also reduces norcraugsodine to norbelladine with a 400-fold lower specific activity. These studies identify a missing step in the biosynthesis of this pharmacologically important class of plant natural products.

PubMed: 27252378
DOI: 10.1074/jbc.M116.717827

実験手法

X-RAY DIFFRACTION (1.73 Å)