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| | <StructureSection load='5g6r' size='340' side='right'caption='[[5g6r]], [[Resolution|resolution]] 1.82Å' scene=''> | | <StructureSection load='5g6r' size='340' side='right'caption='[[5g6r]], [[Resolution|resolution]] 1.82Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5g6r]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5G6R OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5G6R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5g6r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_oryzae Aspergillus oryzae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5G6R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5G6R FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.82Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5g6s|5g6s]]</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/2-methyl-1-pyrroline_reductase 2-methyl-1-pyrroline reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.48 1.5.1.48] </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=5g6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g6r OCA], [https://pdbe.org/5g6r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5g6r RCSB], [https://www.ebi.ac.uk/pdbsum/5g6r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5g6r ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5g6r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g6r OCA], [http://pdbe.org/5g6r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5g6r RCSB], [http://www.ebi.ac.uk/pdbsum/5g6r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5g6r ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/REDAM_ASPOR REDAM_ASPOR] NADPH-dependent reductive aminase that catalyzes the reductive coupling of a broad set of carbonyl compounds with a variety of primary and secondary amines (Ref.2). Possesses remarkably high activity for the reductive amination of ketones and amines, often with high stereoselectivity and in some cases with ketone:amine ratios as low as 1:1 (Ref.2). The cofactor NADPH, the carbonyl compound and the amine are added to the enzyme in that sequence, followed by the release of product, NADP(+) being released at last (Ref.2). RedAm is also able to act in the reverse, oxidative direction and exhibits activity in the dehydrogenation of amines to yield imines (Ref.2). The highest activity is found for 1-methyl-tetrahydroquinoline and acyclic amines are also found to be transformed (Ref.2).[REFERENCE:2] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 2-methyl-1-pyrroline reductase]] | + | [[Category: Aspergillus oryzae]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Aleku, G]] | + | [[Category: Aleku G]] |
| - | [[Category: Grogan, G]] | + | [[Category: Grogan G]] |
| - | [[Category: Man, H]] | + | [[Category: Man H]] |
| - | [[Category: Turner, N J]] | + | [[Category: Turner NJ]] |
| - | [[Category: Amine]]
| + | |
| - | [[Category: Imine reductase]]
| + | |
| - | [[Category: Nadph]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
REDAM_ASPOR NADPH-dependent reductive aminase that catalyzes the reductive coupling of a broad set of carbonyl compounds with a variety of primary and secondary amines (Ref.2). Possesses remarkably high activity for the reductive amination of ketones and amines, often with high stereoselectivity and in some cases with ketone:amine ratios as low as 1:1 (Ref.2). The cofactor NADPH, the carbonyl compound and the amine are added to the enzyme in that sequence, followed by the release of product, NADP(+) being released at last (Ref.2). RedAm is also able to act in the reverse, oxidative direction and exhibits activity in the dehydrogenation of amines to yield imines (Ref.2). The highest activity is found for 1-methyl-tetrahydroquinoline and acyclic amines are also found to be transformed (Ref.2).[REFERENCE:2]
Publication Abstract from PubMed
Reductive amination is one of the most important methods for the synthesis of chiral amines. Here we report the discovery of an NADP(H)-dependent reductive aminase from Aspergillus oryzae (AspRedAm, Uniprot code Q2TW47) that can catalyse the reductive coupling of a broad set of carbonyl compounds with a variety of primary and secondary amines with up to >98% conversion and with up to >98% enantiomeric excess. In cases where both carbonyl and amine show high reactivity, it is possible to employ a 1:1 ratio of the substrates, forming amine products with up to 94% conversion. Steady-state kinetic studies establish that the enzyme is capable of catalysing imine formation as well as reduction. Crystal structures of AspRedAm in complex with NADP(H) and also with both NADP(H) and the pharmaceutical ingredient (R)-rasagiline are reported. We also demonstrate preparative scale reductive aminations with wild-type and Q240A variant biocatalysts displaying total turnover numbers of up to 32,000 and space time yields up to 3.73 g l-1 d-1.
A reductive aminase from Aspergillus oryzae.,Aleku GA, France SP, Man H, Mangas-Sanchez J, Montgomery SL, Sharma M, Leipold F, Hussain S, Grogan G, Turner NJ Nat Chem. 2017 Oct;9(10):961-969. doi: 10.1038/nchem.2782. Epub 2017 May 29. PMID:28937665[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Aleku GA, France SP, Man H, Mangas-Sanchez J, Montgomery SL, Sharma M, Leipold F, Hussain S, Grogan G, Turner NJ. A reductive aminase from Aspergillus oryzae. Nat Chem. 2017 Oct;9(10):961-969. doi: 10.1038/nchem.2782. Epub 2017 May 29. PMID:28937665 doi:http://dx.doi.org/10.1038/nchem.2782
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