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Crystal structure of the mitochondrial protein mitoNEET bound to a benze-sulfonide ligand.

ABSTRACT: MitoNEET (gene cisd1) is a mitochondrial outer membrane [2Fe-2S] protein and is a potential drug target in several metabolic diseases. Previous studies have demonstrated that mitoNEET functions as a redox-active and pH-sensing protein that regulates mitochondrial metabolism, although the structural basis of the potential drug binding site(s) remains elusive. Here we report the crystal structure of the soluble domain of human mitoNEET with a sulfonamide ligand, furosemide. Exploration of the high-resolution crystal structure is used to design mitoNEET binding molecules in a pilot study of molecular probes for use in future development of mitochondrial targeted therapies for a wide variety of metabolic diseases, including obesity, diabetes and neurodegenerative diseases such as Alzheimer's and Parkinson's disease.

SUBMITTER: Geldenhuys WJ

PROVIDER: S-EPMC7205193 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Crystal structure of the mitochondrial protein mitoNEET bound to a benze-sulfonide ligand.

Geldenhuys Werner J WJ Long Timothy E TE Saralkar Pushkar P Iwasaki Toshio T Nuñez Raisa A A RAA Nair Rajesh R RR Konkle Mary E ME Menze Michael A MA Pinti Mark V MV Hollander John M JM Hazlehurst Lori A LA Robart Aaron R AR

Communications chemistry 20190703

MitoNEET (gene <i>cisd1</i>) is a mitochondrial outer membrane [2Fe-2S] protein and is a potential drug target in several metabolic diseases. Previous studies have demonstrated that mitoNEET functions as a redox-active and pH-sensing protein that regulates mitochondrial metabolism, although the structural basis of the potential drug binding site(s) remains elusive. Here we report the crystal structure of the soluble domain of human mitoNEET with a sulfonamide ligand, furosemide. Exploration of t ...[more]

PMID: 32382661

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