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==Crystal structure of Imine Reductase Mutant(M5) from Actinoalloteichus hymeniacidonis in complex with NADPH== | ==Crystal structure of Imine Reductase Mutant(M5) from Actinoalloteichus hymeniacidonis in complex with NADPH== | ||
<StructureSection load='7wnw' size='340' side='right'caption='[[7wnw]]' scene=''> | <StructureSection load='7wnw' size='340' side='right'caption='[[7wnw]], [[Resolution|resolution]] 2.13Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WNW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WNW FirstGlance]. <br> | <table><tr><td colspan='2'>[[7wnw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Actinoalloteichus_hymeniacidonis Actinoalloteichus hymeniacidonis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WNW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WNW FirstGlance]. <br> | ||
</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=7wnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wnw OCA], [https://pdbe.org/7wnw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wnw RCSB], [https://www.ebi.ac.uk/pdbsum/7wnw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wnw ProSAT]</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]] 2.13Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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=7wnw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wnw OCA], [https://pdbe.org/7wnw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wnw RCSB], [https://www.ebi.ac.uk/pdbsum/7wnw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wnw ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A1D8BXU6_9PSEU A0A1D8BXU6_9PSEU] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Although imine reductases (IREDs) are emerging as attractive reductive aminases (RedAms), their substrate scope is still narrow, and rational engineering is rare. Focusing on hydrogen bond reorganization and cavity expansion, a concise strategy combining rational cavity design, combinatorial active-site saturation test (CAST), and thermostability engineering was designed, that transformed the weakly active IR-G36 into a variant M5 with superior performance for the synthesis of (R)-3-benzylamino-1-Boc-piperidine, with a 4193-fold improvement in catalytic efficiency, a 16.2 improvement in Tm, and a significant increase in the e.e. value from 78% (R) to >99% (R). M5 exhibits broad substrate scope for the synthesis of diverse azacycloalkylamines, and the reaction was demonstrated on a hectogram-scale under industrially relevant conditions. Our study provides a compelling example of the preparation of versatile and efficient IREDs, with exciting opportunities in medicinal and process chemistry as well as synthetic biology. | |||
Tuning an Imine Reductase for the Asymmetric Synthesis of Azacycloalkylamines by Concise Structure-Guided Engineering.,Zhang J, Liao D, Chen R, Zhu F, Ma Y, Gao L, Qu G, Cui C, Sun Z, Lei X, Gao S Angew Chem Int Ed Engl. 2022 Mar 23. doi: 10.1002/anie.202201908. PMID:35322515<ref>PMID:35322515</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7wnw" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Actinoalloteichus hymeniacidonis]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chen R]] | [[Category: Chen R]] | ||
[[Category: Gao S]] | [[Category: Gao S]] | ||
[[Category: Zhand J]] | [[Category: Zhand J]] | ||
Latest revision as of 20:42, 29 November 2023
Crystal structure of Imine Reductase Mutant(M5) from Actinoalloteichus hymeniacidonis in complex with NADPHCrystal structure of Imine Reductase Mutant(M5) from Actinoalloteichus hymeniacidonis in complex with NADPH
Structural highlights
FunctionPublication Abstract from PubMedAlthough imine reductases (IREDs) are emerging as attractive reductive aminases (RedAms), their substrate scope is still narrow, and rational engineering is rare. Focusing on hydrogen bond reorganization and cavity expansion, a concise strategy combining rational cavity design, combinatorial active-site saturation test (CAST), and thermostability engineering was designed, that transformed the weakly active IR-G36 into a variant M5 with superior performance for the synthesis of (R)-3-benzylamino-1-Boc-piperidine, with a 4193-fold improvement in catalytic efficiency, a 16.2 improvement in Tm, and a significant increase in the e.e. value from 78% (R) to >99% (R). M5 exhibits broad substrate scope for the synthesis of diverse azacycloalkylamines, and the reaction was demonstrated on a hectogram-scale under industrially relevant conditions. Our study provides a compelling example of the preparation of versatile and efficient IREDs, with exciting opportunities in medicinal and process chemistry as well as synthetic biology. Tuning an Imine Reductase for the Asymmetric Synthesis of Azacycloalkylamines by Concise Structure-Guided Engineering.,Zhang J, Liao D, Chen R, Zhu F, Ma Y, Gao L, Qu G, Cui C, Sun Z, Lei X, Gao S Angew Chem Int Ed Engl. 2022 Mar 23. doi: 10.1002/anie.202201908. PMID:35322515[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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