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Structure, Activity and Stereoselectivity of NADPH-Dependent Oxidoreductases Catalysing the S-Selective Reduction of the Imine Substrate 2-Methylpyrroline

DOI: 10.1002/cbic.201402625 DOI Help
PMID: 25809902 PMID Help

Authors: Henry Man (University of York) , Elizabeth Wells (University of York) , Shahed Hussain (University of Manchester) , Friedemann Leipold (University of Manchester) , Sam Hart (University of York) , Johan Turkenburg (University of York) , Nicholas J. Turner (University of Manchester) , Gideon Grogan (University of York)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Chembiochem , VOL 16 , PAGES 1052 - 1059

State: Published (Approved)
Published: May 2015

Abstract: Oxidoreductases from Streptomyces sp. GF3546 [3546-IRED], Bacillus cereus BAG3X2 (BcIRED) and Nocardiopsis halophila (NhIRED) each reduce prochiral 2-methylpyrroline (2MPN) to (S)-2-methylpyrrolidine with >95 % ee and also a number of other imine substrates with good selectivity. Structures of BcIRED and NhIRED have helped to identify conserved active site residues within this subgroup of imine reductases that have S selectivity towards 2MPN, including a tyrosine residue that has a possible role in catalysis and superimposes with an aspartate in related enzymes that display R selectivity towards the same substrate. Mutation of this tyrosine residue—Tyr169—in 3546-IRED to Phe resulted in a mutant of negligible activity. The data together provide structural evidence for the location and significance of the Tyr residue in this group of imine reductases, and permit a comparison of the active sites of enzymes that reduce 2MPN with either R or S selectivity.

Journal Keywords: amines;asymmetric catalysis;imines;IREDs;NADPH;oxidoreductases

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 16/12/2015 14:10

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