Improved Homology Model of the Human all-trans Retinoic Acid Metabolizing Enzyme CYP26A1.

ABSTRACT: A new CYP26A1 homology model was built based on the crystal structure of cyanobacterial CYP120A1. The model quality was examined for stereochemical accuracy, folding reliability, and absolute quality using a variety of different bioinformatics tools. Furthermore, the docking capabilities of the model were assessed by docking of the natural substrate all-trans-retinoic acid (atRA), and a group of known azole- and tetralone-based CYP26A1 inhibitors. The preferred binding pose of atRA suggests the (4S)-OH-atRA metabolite production, in agreement with recently available experimental data. The distances between the ligands and the heme group iron of the enzyme are in agreement with corresponding distances obtained for substrates and azole inhibitors for other cytochrome systems. The calculated

SUBMITTER: Awadalla MK 

PROVIDER: S-EPMC6274249 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature