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| | <StructureSection load='7mbf' size='340' side='right'caption='[[7mbf]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='7mbf' size='340' side='right'caption='[[7mbf]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7mbf]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MBF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MBF FirstGlance]. <br> | + | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MBF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MBF FirstGlance]. <br> |
| - | </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Codeinone_reductase_(NADPH) Codeinone reductase (NADPH)], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.247 1.1.1.247] </span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</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=7mbf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mbf OCA], [https://pdbe.org/7mbf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mbf RCSB], [https://www.ebi.ac.uk/pdbsum/7mbf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mbf ProSAT]</span></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=7mbf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mbf OCA], [https://pdbe.org/7mbf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mbf RCSB], [https://www.ebi.ac.uk/pdbsum/7mbf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mbf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Function == | |
| - | [[https://www.uniprot.org/uniprot/COR13_PAPSO COR13_PAPSO]] Reduces codeinone to codeine in the penultimate step in morphine biosynthesis. Can use morphinone, hydrocodone and hydromorphone as substrate during reductive reaction with NADPH as cofactor, and morphine and dihydrocodeine as substrate during oxidative reaction with NADP as cofactor.<ref>PMID:10417697</ref> | |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Carr, S C]] | + | [[Category: Carr SC]] |
| - | [[Category: Ng, K K.S]] | + | [[Category: Ng KKS]] |
| - | [[Category: Aldo-keto reductase]]
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| - | [[Category: Benzylisoquinoline alkaloid]]
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| - | [[Category: Biosynthesis]]
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| - | [[Category: Opium poppy]]
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| - | [[Category: Oxidoreductase]]
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| Structural highlights
Publication Abstract from PubMed
Benzylisoquinoline alkaloids (BIAs) are a class of specialized metabolites with a diverse range of chemical structures and physiological effects. Codeine and morphine are two closely related BIAs with particularly useful analgesic properties. The aldo-keto reductase (AKR) codeinone reductase (COR) catalyzes the final and penultimate steps in the biosynthesis of codeine and morphine, respectively, in opium poppy (Papaver somniferum). However, the structural determinants that mediate substrate recognition and catalysis are not well defined. Here, we describe the crystal structure of apo-COR determined to a resolution of 2.4 A by molecular replacement using chalcone reductase as a search model. Structural comparisons of COR to closely related plant AKRs and more distantly related homologues reveal a novel conformation in the beta1alpha1 loop adjacent to the BIA binding pocket. The proximity of this loop to several highly conserved active-site residues and the expected location of the nicotinamide ring of the NADP(H) cofactor suggest a model for BIA recognition that implies roles for several key residues. Using site-directed mutagenesis, we show that substitutions at Met-28 and His-120 of COR lead to changes in AKR activity for the major and minor substrates codeinone and neopinone, respectively. Our findings provide a framework for understanding the molecular basis of substrate recognition in COR and the closely related 1,2-dehydroreticuline reductase responsible for the second half of a stereochemical inversion that initiates the morphine biosynthesis pathway.
Structural studies of codeinone reductase reveal novel insights into aldo-keto reductase function in benzylisoquinoline alkaloid biosynthesis.,Carr SC, Torres MA, Morris JS, Facchini PJ, Ng KKS J Biol Chem. 2021 Sep 18:101211. doi: 10.1016/j.jbc.2021.101211. PMID:34547292[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Carr SC, Torres MA, Morris JS, Facchini PJ, Ng KKS. Structural studies of codeinone reductase reveal novel insights into aldo-keto reductase function in benzylisoquinoline alkaloid biosynthesis. J Biol Chem. 2021 Sep 18:101211. doi: 10.1016/j.jbc.2021.101211. PMID:34547292 doi:http://dx.doi.org/10.1016/j.jbc.2021.101211
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