5FEU
Noroxomaritidine/Norcraugsodine Reductase in complex with NADP+
Summary for 5FEU
| Entry DOI | 10.2210/pdb5feu/pdb |
| Related | 5FF9 5FFF |
| Descriptor | Noroxomaritidine/Norcraugsodine Reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total) |
| Functional Keywords | short-chain dehydrogenase/reductase alkaloid biosynthesis, oxidoreductase |
| Biological source | Narcissus pseudonarcissus |
| Total number of polymer chains | 1 |
| Total formula weight | 31930.65 |
| Authors | Holland, C.,Jez, J.M. (deposition date: 2015-12-17, release date: 2016-06-08, Last modification date: 2023-09-27) |
| Primary citation | 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 Cited by 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: 27252378DOI: 10.1074/jbc.M116.717827 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.73 Å) |
Structure validation
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