Molecular dynamics study on the hydrogen bond formation between α-hydrogen atom of L-Phe and N5 atom of FAD in the enzyme-substrate complex of the L-Phe oxidase reaction

Abstract

It is difficult to observe the structure of the enzyme-substrate complex (ES complex) experimentally, since the complex changes to the enzyme and its product during observation. The molecular dynamics (MD) approach is ideal to observe the structural change of enzyme and of substrate in the ES complex. Analyses on the complex of L-Phe oxidase with L-Phe by MD showed 1) the distance between the α-hydrogen atom of L-Phe and the N5 atom of isoalloxazine ring of FAD to be 2.64 ± 0.19 Å, and 2) the angle CA-HA-N5 atoms to be 141.5 ± 10.7°. This result clearly showed that the α-hydrogen atom forms the hydrogen bond with the N5 atom of isoalloxazine ring of FAD in the enzyme-substrate complex. Thus, the complex is ready for the hydrogen transfer from substrate to FAD in the key step of the oxidation of substrate by the enzyme.