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7mbf

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codeinone reductase isoform 1.3 Apo form

Structural highlights

7mbf is a 6 chain structure with sequence from Papaver somniferum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Unterlinner B, Lenz R, Kutchan TM. Molecular cloning and functional expression of codeinone reductase: the penultimate enzyme in morphine biosynthesis in the opium poppy Papaver somniferum. Plant J. 1999 Jun;18(5):465-75. PMID:10417697
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7mbf"

Categories: Large Structures | Papaver somniferum | Carr SC | Ng KKS

@@ Line 3: / Line 3: @@
 <StructureSection load='7mbf' size='340' side='right'caption='[[7mbf]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == 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'>[[7mbf]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Papaver_somniferum Papaver somniferum]. 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]] 2.4&#8491;</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>
 == 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>
+[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;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Carr, S C]]
+[[Category: Papaver somniferum]]
-[[Category: Ng, K K.S]]
+[[Category: Carr SC]]
-[[Category: Aldo-keto reductase]]
+[[Category: Ng KKS]]
-[[Category: Benzylisoquinoline alkaloid]]
-[[Category: Biosynthesis]]
-[[Category: Opium poppy]]
-[[Category: Oxidoreductase]]

7mbf

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Current revision

codeinone reductase isoform 1.3 Apo form

Structural highlights

Function

Publication Abstract from PubMed

References

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