Crystal Structure of the Mitochondrial Protein MitoNEET Bound to a Benze-sulfonide Ligand

Overview

Journal Commun Chem

Publisher Springer Nature

Specialty Chemistry

Date 2020 May 9

PMID 32382661

Citations 13

Authors

Werner J Geldenhuys

Timothy E Long

Pushkar Saralkar

Toshio Iwasaki

Raisa A A Nunez

Rajesh R Nair

Mary E Konkle

Michael A Menze

Mark V Pinti

John M Hollander

Lori A Hazlehurst

Aaron R Robart

Affiliations

Soon will be listed here.

Abstract

MitoNEET (gene ) 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.

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