Identification of promiscuous ene-reductase activity by mining structural databases using active site constellations.

ABSTRACT: The exploitation of catalytic promiscuity and the application of de novo design have recently opened the access to novel, non-natural enzymatic activities. Here we describe a structural bioinformatic method for predicting catalytic activities of enzymes based on three-dimensional constellations of functional groups in active sites ('catalophores'). As a proof-of-concept we identify two enzymes with predicted promiscuous ene-reductase activity (reduction of activated C-C double bonds) and compare them with known ene-reductases, that is, members of the Old Yellow Enzyme family. Despite completely different amino acid sequences, overall structures and protein folds, high-resolution crystal structures reveal equivalent binding modes of typical Old Yellow Enzyme substrates and ligands. Biochemi

SUBMITTER: Steinkellner G 

PROVIDER: S-EPMC4083419 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature