Author ORCID Identifier

https://orcid.org/0000-0001-9562-4649

https://orcid.org/0000-0003-0959-3714

https://orcid.org/0000-0002-0518-3972

Document Type

Article

Publication Date

2019

College/Unit

School of Pharmacy

Department/Program/Center

Pharmaceutical Sciences

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.

Source Citation

Geldenhuys, W.J., Long, T.E., Saralkar, P. et al. Crystal structure of the mitochondrial protein mitoNEET bound to a benze-sulfonide ligand. Commun Chem 2, 77 (2019). https://doi.org/10.1038/s42004-019-0172-x

Comments

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.

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