5ff9: Difference between revisions
New page: '''Unreleased structure''' The entry 5ff9 is ON HOLD Authors: Jez, J.M., Holland, C.K. Description: Noroxomaritidine/Norcraugsodine Reductase Category: Unreleased Structures [[Cate... |
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==Noroxomaritidine/Norcraugsodine Reductase in Complex with NADP+ and tyramine== | |||
<StructureSection load='5ff9' size='340' side='right'caption='[[5ff9]], [[Resolution|resolution]] 1.81Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ff9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Narcissus_pseudonarcissus Narcissus pseudonarcissus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FF9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FF9 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.814Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AEF:4-(2-AMINOETHYL)PHENOL'>AEF</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ff9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ff9 OCA], [https://pdbe.org/5ff9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ff9 RCSB], [https://www.ebi.ac.uk/pdbsum/5ff9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ff9 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/NR_NARPS NR_NARPS] In the Amaryllidaceae alkaloids biosynthesic pathway, catalyzes the conversion of noroxomaritidine to oxomaritidine, a precursor of haemanthamine- and crinamine-type alkaloids, promising anticancer agents (PubMed:27252378). Can also, to some extent, catalyze the condensation of 3,4-dihydroxybenzaldehyde (3,4-DHBA) and tyramine to produce norbelladine, and of isovanillin and tyramine to produce 4'-O-methylnorbelladine (PubMed:27252378).<ref>PMID:27252378</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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 haemanthamine 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 haemanthamine 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 E. 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. | |||
Identification of a Noroxomaritidine Reductase with Amaryllidaceae Alkaloid Biosynthesis Related Activities.,Kilgore MB, Holland CK, Jez JM, Kutchan TM J Biol Chem. 2016 Jun 1. pii: jbc.M116.717827. PMID:27252378<ref>PMID:27252378</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5ff9" style="background-color:#fffaf0;"></div> | ||
[[Category: Holland | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Narcissus pseudonarcissus]] | |||
[[Category: Holland CK]] | |||
[[Category: Jez JM]] | |||