Semi-Rational Design of L-Isoleucine Dioxygenase Generated Its Activity for Aromatic Amino Acid Hydroxylation.

ABSTRACT: Fe (II)-and 2-ketoglutarate-dependent dioxygenases (Fe (II)/α-KG DOs) have been applied to catalyze hydroxylation of amino acids. However, the Fe (II)/α-KG DOs that have been developed and characterized are not sufficient. L-isoleucine dioxygenase (IDO) is an Fe (II)/α-KG DO that specifically catalyzes the formation of 4-hydroxyisoleucine (4-HIL) from L-isoleucine (L-Ile) and exhibits a substrate specificity toward L-aliphatic amino acids. To expand the substrate spectrum of IDO toward aromatic amino acids, in this study, we analyzed the regularity of the substrate spectrum of IDO using molecular dynamics (MD) simulation and found that the distance between Fe²⁺, C2 of α-KG and amino acid chain's C4 may be critical for regulating the substrate specificity of the enzyme. The mutat

SUBMITTER: An J 

PROVIDER: S-EPMC10180240 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature