Ligand tunnels in T. brucei and human CYP51: Insights for parasite-specific drug design.

ABSTRACT:

Background

Cytochrome P450 sterol 14α-demethylase (CYP51) is an essential enzyme for sterol biosynthesis and a target for anti-parasitic drug design. However, the design of parasite-specific drugs that inhibit parasitic CYP51 without severe side effects remains challenging. The active site of CYP51 is situated in the interior of the protein. Here, we characterize the potential ligand egress routes and mechanisms in Trypanosoma brucei and human CYP51 enzymes.

Methods

We performed Random Acceleration Molecular Dynamics simulations of the egress of four different ligands from the active site of models of soluble and membrane-bound T. brucei CYP51 and of soluble human CYP51.

Results

In the simulations, tunnel 2f, which leads to the membrane, was found to be the predominan

SUBMITTER: Yu X 

PROVIDER: S-EPMC4689311 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature