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

Geldenhuys, Werner J.; Long, Timothy E.; Saralkar, Pushkar; Iwasaki, Toshio; Nuñez, Raisa A.; Nair, Rajesh R.; Konkle, Mary E.; Menze, Michael A.; Pinti, Mark V.; Hollander, John M.; Hazlehurst, Lori A.; Robart, Aaron R.

doi:10.1038/s42004-019-0172-x

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

Journal Article · Wed Jul 03 00:00:00 EDT 2019 · Communications Chemistry

DOI:https://doi.org/10.1038/s42004-019-0172-x· OSTI ID:1557303

Geldenhuys, Werner J. ^[1]; Long, Timothy E. ^[2]; Saralkar, Pushkar ^[1]; ^[3]; Nuñez, Raisa A. ^[1]; Nair, Rajesh R. ^[1]; ^[4]; Menze, Michael A. ^[5]; Pinti, Mark V. ^[1]; Hollander, John M. ^[1]; Hazlehurst, Lori A. ^[6]; ^[1]

West Virginia Univ., Morgantown, WV (United States)
Marshall Univ., Huntington, WV (United States)
Nippon Medical School, Sendagi, Tokyo (Japan)
Ball State Univ., Muncie, IN (United States)
Univ. of Louisville, KY (United States)
West Virginia Univ., Morgantown, WV (United States); Modulation Therapeutics, Morgantown, WV (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institute of Health (NIH); National Institute of General Medical Sciences (NIGMS); Office of Research Infrastructure Programs (ORIP); USDOE Office of Science (SC); Ohio Valley Whipkey Trust

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1557303

Journal Information:: Communications Chemistry, Journal Name: Communications Chemistry Journal Issue: 1 Vol. 2; ISSN 2399-3669

Publisher:: Springer NatureCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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