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

Authors

Werner J. Geldenhuys, est Virginia UniversityFollow
Timothy E. long, Marshall University
Pushkar Saralkar, West Virginia University
Toshio Iwasaki, Nippon Medical School, Sendagi, Tokyo
Rasia A. A. Nuñez, School of Medicine West Virginia University
Rajesh R. Nair, School of Medicine West Virginia University
Mary E. Konkle, Ball State University
Michael A. Menze, University of Louisville
Mark V. Pinti, School of Medicine West Virginia University
John M. Hollander, School of Medicine West Virginia University
Lori A. Hazlehurst, School of Pharmacy West Virginia University
Aaron R. Robart, School of Medicine West Virginia University, MorgantownFollow

Author ORCID Identifier

N/A

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

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

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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.

Digital Commons Citation

Geldenhuys, Werner J.; long, Timothy E.; Saralkar, Pushkar; Iwasaki, Toshio; Nuñez, Rasia A. A.; Nair, Rajesh R.; Konkle, Mary E.; Menze, Michael A.; Pinti, Mark V.; Hollander, John M.; Hazlehurst, Lori A.; and Robart, Aaron R., "Crystal Structure of the Mitochondrial Protein mitoNEET Bound to a Benze-sulfonide Ligand" (2019). Faculty & Staff Scholarship. 1965.
https://researchrepository.wvu.edu/faculty_publications/1965

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

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