Systematic Evaluation of Imine-Reducing Enzymes: Common Principles in Imine Reductases, β-Hydroxy Acid Dehydrogenases, and Short-Chain Dehydrogenases/ Reductases.

ABSTRACT: The enzymatic, asymmetric reduction of imines is catalyzed by imine reductases (IREDs), members of the short-chain dehydrogenase/reductase (SDR) family, and β-hydroxy acid dehydrogenase (βHAD) variants. Systematic evaluation of the structures and substrate-binding sites of the three enzyme families has revealed four common principles for imine reduction: structurally conserved cofactor-binding domains; tyrosine, aspartate, or glutamate as proton donor; at least four characteristic flanking residues that adapt the donor's pK_a and polarize the substrate; and a negative electrostatic potential in the substrate-binding site to stabilize the transition state. As additional catalytically relevant positions, we propose alternative proton donors in IREDs and βHADs as well as proton rela

SUBMITTER: Stockinger P 

PROVIDER: S-EPMC7540600 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature