Structure, Activity and Stereoselectivity of NADPH‐Dependent Oxidoreductases Catalysing the <i>S</i>‐Selective Reduction of the Imine Substrate 2‐Methylpyrroline

DOI Web Site Web Site 1 Citations

Description

<jats:title>Abstract</jats:title><jats:p>Oxidoreductases from <jats:italic>Streptomyces</jats:italic> sp. GF3546 [3546‐IRED], <jats:italic>Bacillus cereus</jats:italic> BAG3X2 (<jats:italic>Bc</jats:italic>IRED) and <jats:italic>Nocardiopsis halophila</jats:italic> (<jats:italic>Nh</jats:italic>IRED) each reduce prochiral 2‐methylpyrroline (2MPN) to (<jats:italic>S</jats:italic>)‐2‐methylpyrrolidine with >95 % <jats:italic>ee</jats:italic> and also a number of other imine substrates with good selectivity. Structures of <jats:italic>Bc</jats:italic>IRED and <jats:italic>Nh</jats:italic>IRED have helped to identify conserved active site residues within this subgroup of imine reductases that have <jats:italic>S</jats:italic> selectivity towards 2MPN, including a tyrosine residue that has a possible role in catalysis and superimposes with an aspartate in related enzymes that display <jats:italic>R</jats:italic> 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 <jats:italic>R</jats:italic> or <jats:italic>S</jats:italic> selectivity.</jats:p>

Journal

  • ChemBioChem

    ChemBioChem 16 (7), 1052-1059, 2015-03-24

    Wiley

Citations (1)*help

See more

Report a problem

Back to top