7V62

Crystal structure of human OSBP ORD in complex with cholesterol

7V62 の概要

• エントリーDOI: 10.2210/pdb7v62/pdb
• 分子名称: Oxysterol-binding protein 1, CHOLESTEROL, 2,3-DIHYDROXY-1,4-DITHIOBUTANE, ... (6 entities in total)
• 機能のキーワード: lipid binding protein, lipid transport protein, oxysterol binding protein, oxysterol binding protein-related domain, lipid transport
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 190641.56

構造登録者

Kobayashi, J.,Kato, R. (登録日: 2021-08-19, 公開日: 2022-06-08, 最終更新日: 2025-09-17)

主引用文献

Kobayashi, J.,Arita, M.,Sakai, S.,Kojima, H.,Senda, M.,Senda, T.,Hanada, K.,Kato, R.
Ligand Recognition by the Lipid Transfer Domain of Human OSBP Is Important for Enterovirus Replication.
Acs Infect Dis., 8:1161-1170, 2022

PubMed Abstract: Oxysterol-binding protein (OSBP), which transports cholesterol and phosphatidylinositol 4-monophosphate (PtdIns[4]P) between different organelles, serves as a conserved host factor for the replication of various viruses, and OSBP inhibitors exhibit antiviral effects. Here, we determined the crystal structure of the lipid transfer domain of human OSBP in complex with endogenous cholesterol. The hydrocarbon tail and tetracyclic ring of cholesterol interact with the hydrophobic tunnel of OSBP, and the hydroxyl group of cholesterol forms a hydrogen bond network at the bottom of the tunnel. Systematic mutagenesis of the ligand-binding region revealed that M446W and L590W substitutions confer functional tolerance to an OSBP inhibitor, T-00127-HEV2. Employing the M446W variant as a functional replacement for the endogenous OSBP in the presence of T-00127-HEV2, we have identified previously unappreciated amino acid residues required for viral replication. The combined use of the inhibitor and the OSBP variant will be useful in elucidating the enigmatic in vivo functions of OSBP.

PubMed: 35613096
DOI: 10.1021/acsinfecdis.2c00108

実験手法

X-RAY DIFFRACTION (3.25 Å)