Controlling the Substrate Specificity of an Enzyme through Structural Flexibility by Varying the Salt-Bridge Density.

ABSTRACT: Many enzymes, particularly in one single family, with highly conserved structures and folds exhibit rather distinct substrate specificities. The underlying mechanism remains elusive, the resolution of which is of great importance for biochemistry, biophysics, and bioengineering. Here, we performed a neutron scattering experiment and molecular dynamics (MD) simulations on two structurally similar CYP450 proteins; CYP101 primarily catalyzes one type of ligands, then CYP2C9 can catalyze a large range of substrates. We demonstrated that it is the high density of salt bridges in CYP101 that reduces its structural flexibility, which controls the ligand access channel and the fluctuation of the catalytic pocket, thus restricting its selection on substrates. Moreover, we performed MD simulations o

SUBMITTER: Huang J 

PROVIDER: S-EPMC8470667 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature