7A3W
Structure of Imine Reductase from Pseudomonas sp.
Summary for 7A3W
| Entry DOI | 10.2210/pdb7a3w/pdb |
| Descriptor | NAD(P)-dependent oxidoreductase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 1,2-ETHANEDIOL, ... (5 entities in total) |
| Functional Keywords | imine, enimine, nadph, oxidoreductase |
| Biological source | Pseudomonas putida |
| Total number of polymer chains | 2 |
| Total formula weight | 63917.70 |
| Authors | Cuetos, A.,Thorpe, T.,Turner, N.J.,Grogan, G. (deposition date: 2020-08-18, release date: 2021-08-25, Last modification date: 2024-02-07) |
| Primary citation | Thorpe, T.W.,Marshall, J.R.,Harawa, V.,Ruscoe, R.E.,Cuetos, A.,Finnigan, J.D.,Angelastro, A.,Heath, R.S.,Parmeggiani, F.,Charnock, S.J.,Howard, R.M.,Kumar, R.,Daniels, D.S.B.,Grogan, G.,Turner, N.J. Multifunctional biocatalyst for conjugate reduction and reductive amination. Nature, 604:86-91, 2022 Cited by PubMed Abstract: Chiral amine diastereomers are ubiquitous in pharmaceuticals and agrochemicals, yet their preparation often relies on low-efficiency multi-step synthesis. These valuable compounds must be manufactured asymmetrically, as their biochemical properties can differ based on the chirality of the molecule. Herein we characterize a multifunctional biocatalyst for amine synthesis, which operates using a mechanism that is, to our knowledge, previously unreported. This enzyme (EneIRED), identified within a metagenomic imine reductase (IRED) collection and originating from an unclassified Pseudomonas species, possesses an unusual active site architecture that facilitates amine-activated conjugate alkene reduction followed by reductive amination. This enzyme can couple a broad selection of α,β-unsaturated carbonyls with amines for the efficient preparation of chiral amine diastereomers bearing up to three stereocentres. Mechanistic and structural studies have been carried out to delineate the order of individual steps catalysed by EneIRED, which have led to a proposal for the overall catalytic cycle. This work shows that the IRED family can serve as a platform for facilitating the discovery of further enzymatic activities for application in synthetic biology and organic synthesis. PubMed: 35388195DOI: 10.1038/s41586-022-04458-x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.59 Å) |
Structure validation
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