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| | ==The structure of salutaridine reductase from Papaver somniferum.== | | ==The structure of salutaridine reductase from Papaver somniferum.== |
| - | <StructureSection load='3o26' size='340' side='right' caption='[[3o26]], [[Resolution|resolution]] 1.91Å' scene=''> | + | <StructureSection load='3o26' size='340' side='right'caption='[[3o26]], [[Resolution|resolution]] 1.91Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3o26]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Papaver_somniferum Papaver somniferum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O26 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O26 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3o26]] is a 1 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=3O26 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O26 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></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]] 1.91Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Salutaridine_reductase_(NADPH) Salutaridine reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.248 1.1.1.248] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3o26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o26 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3o26 RCSB], [http://www.ebi.ac.uk/pdbsum/3o26 PDBsum]</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=3o26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o26 OCA], [https://pdbe.org/3o26 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o26 RCSB], [https://www.ebi.ac.uk/pdbsum/3o26 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o26 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/SALR_PAPSO SALR_PAPSO] Short-chain dehydrogenases/reductases involved in biosynthesis of morphinan-type benzylisoquinoline and opiate alkaloids natural products (PubMed:22098111). Catalyzes specifically the stereospecific conversion of salutaridine to salutaridinol (PubMed:22098111).<ref>PMID:16968522</ref> <ref>PMID:19648114</ref> <ref>PMID:22098111</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3o26" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Papaver somniferum]] | | [[Category: Papaver somniferum]] |
| - | [[Category: Higashi, Y]] | + | [[Category: Higashi Y]] |
| - | [[Category: Kutchen, T M]] | + | [[Category: Kutchen TM]] |
| - | [[Category: Smith, T J]] | + | [[Category: Smith TJ]] |
| - | [[Category: Oxidoreductase]]
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| - | [[Category: Short chain dehydrogenase/reductase]]
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| Structural highlights
Function
SALR_PAPSO Short-chain dehydrogenases/reductases involved in biosynthesis of morphinan-type benzylisoquinoline and opiate alkaloids natural products (PubMed:22098111). Catalyzes specifically the stereospecific conversion of salutaridine to salutaridinol (PubMed:22098111).[1] [2] [3]
Publication Abstract from PubMed
The opium poppy (Papaver somniferum L.) is one of the oldest known medicinal plants. In the biosynthetic pathway for morphine and codeine, salutaridine is reduced to salutaridinol by salutaridine reductase (SalR; EC 1.1.1.248) using NADPH as coenzyme. Here we report the atomic structure of SalR to a resolution of ~1.9A in the presence of NADPH. The core structure is highly homologous to the other members of the short chain dehydrogenase/reductase (SDR) family. The major difference is that the nicotinamide moiety and the substrate-binding pocket are covered by a loop (residues 265-279) and on top of that lies a large 'flap' like domain (residues 105-140). This configuration appears to be a combination of the two common structural themes found in other members of the SDR family. Previous modeling studies suggested that substrate inhibition is due mutually exclusive productive and nonproductive modes of substrate binding in the active site. This model was tested via site-directed mutagenesis and a number of these mutations abrogated substrate inhibition. However, the atomic structure of SalR shows that these mutated residues are, instead, distributed over a wide area of the enzyme and many are not in the active site. To explain how residues distal to the active site might affect catalysis, a model is presented whereby SalR may undergo significant conformational changes during catalytic turnover.
The atomic structure of salutaridine reductase from the opium poppy Papaver somniferum.,Higashi Y, Kutchan TM, Smith TJ J Biol Chem. 2010 Dec 17. PMID:21169353[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ziegler J, Voigtländer S, Schmidt J, Kramell R, Miersch O, Ammer C, Gesell A, Kutchan TM. Comparative transcript and alkaloid profiling in Papaver species identifies a short chain dehydrogenase/reductase involved in morphine biosynthesis. Plant J. 2006 Oct;48(2):177-92. PMID:16968522 doi:10.1111/j.1365-313X.2006.02860.x
- ↑ Ziegler J, Brandt W, Geissler R, Facchini PJ. Removal of substrate inhibition and increase in maximal velocity in the short chain dehydrogenase/reductase salutaridine reductase involved in morphine biosynthesis. J Biol Chem. 2009 Sep 25;284(39):26758-67. PMID:19648114 doi:10.1074/jbc.M109.030957
- ↑ Wijekoon CP, Facchini PJ. Systematic knockdown of morphine pathway enzymes in opium poppy using virus-induced gene silencing. Plant J. 2012 Mar;69(6):1052-63. PMID:22098111 doi:10.1111/j.1365-313X.2011.04855.x
- ↑ Higashi Y, Kutchan TM, Smith TJ. The atomic structure of salutaridine reductase from the opium poppy Papaver somniferum. J Biol Chem. 2010 Dec 17. PMID:21169353 doi:10.1074/jbc.M110.168633
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