Structural basis for human sterol isomerase in cholesterol biosynthesis and multidrug recognition.

ABSTRACT: 3-β-hydroxysteroid-Δ⁸, Δ⁷-isomerase, known as Emopamil-Binding Protein (EBP), is an endoplasmic reticulum membrane protein involved in cholesterol biosynthesis, autophagy, oligodendrocyte formation. The mutation on EBP can cause Conradi-Hunermann syndrome, an inborn error. Interestingly, EBP binds an abundance of structurally diverse pharmacologically active compounds, causing drug resistance. Here, we report two crystal structures of human EBP, one in complex with the anti-breast cancer drug tamoxifen and the other in complex with the cholesterol biosynthesis inhibitor U18666A. EBP adopts an unreported fold involving five transmembrane-helices (TMs) that creates a membrane cavity presenting a pharmacological binding site that accommodates multiple different ligands.

SUBMITTER: Long T 

PROVIDER: S-EPMC6549186 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature