Structural basis for itraconazole-mediated NPC1 inhibition

Tao Long; Xiaofeng Qi; Abdirahman Hassan; Qiren Liang; Jef K. De Brabander; Xiaochun Li

doi:10.1038/s41467-019-13917-5

Nature Communications (Jan 2020)

Structural basis for itraconazole-mediated NPC1 inhibition

Tao Long,
Xiaofeng Qi,
Abdirahman Hassan,
Qiren Liang,
Jef K. De Brabander,
Xiaochun Li

Affiliations

Tao Long: Department of Molecular Genetics, University of Texas Southwestern Medical Center
Xiaofeng Qi: Department of Molecular Genetics, University of Texas Southwestern Medical Center
Abdirahman Hassan: Department of Molecular Genetics, University of Texas Southwestern Medical Center
Qiren Liang: Department of Biochemistry, University of Texas Southwestern Medical Center
Jef K. De Brabander: Department of Biochemistry, University of Texas Southwestern Medical Center
Xiaochun Li: Department of Molecular Genetics, University of Texas Southwestern Medical Center

DOI: https://doi.org/10.1038/s41467-019-13917-5
Journal volume & issue: Vol. 11, no. 1
pp. 1 – 11

Abstract

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Niemann-Pick C1 (NPC1) exports low-density-lipoprotein (LDL)-derived cholesterol from lysosomes and comporses a Sterol-Sensing Domain (SSD). Here authors report a cryo-EM structure of human NPC1 bound to itraconazole which reveals how this binding site in the center of NPC1 blocks a putative lumenal tunnel linked to the SSD.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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