| Structural highlights
Function
CISD1_HUMAN Plays a key role in regulating maximal capacity for electron transport and oxidative phosphorylation (By similarity). May be involved in Fe-S cluster shuttling and/or in redox reactions.[1] [2]
Publication Abstract from PubMed
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.
Crystal structure of the mitochondrial protein mitoNEET bound to a benze-sulfonide ligand.,Geldenhuys WJ, Long TE, Saralkar P, Iwasaki T, Nunez RAA, Nair RR, Konkle ME, Menze MA, Pinti MV, Hollander JM, Hazlehurst LA, Robart AR Commun Chem. 2019;2. doi: 10.1038/s42004-019-0172-x. Epub 2019 Jul 3. PMID:32382661[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wiley SE, Paddock ML, Abresch EC, Gross L, van der Geer P, Nechushtai R, Murphy AN, Jennings PA, Dixon JE. The outer mitochondrial membrane protein mitoNEET contains a novel redox-active 2Fe-2S cluster. J Biol Chem. 2007 Aug 17;282(33):23745-9. Epub 2007 Jun 21. PMID:17584744 doi:C700107200
- ↑ Paddock ML, Wiley SE, Axelrod HL, Cohen AE, Roy M, Abresch EC, Capraro D, Murphy AN, Nechushtai R, Dixon JE, Jennings PA. MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone. Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14342-7. Epub 2007 Aug 31. PMID:17766440
- ↑ Geldenhuys WJ, Long TE, Saralkar P, Iwasaki T, Nunez RAA, Nair RR, Konkle ME, Menze MA, Pinti MV, Hollander JM, Hazlehurst LA, Robart AR. Crystal structure of the mitochondrial protein mitoNEET bound to a benze-sulfonide ligand. Commun Chem. 2019;2. doi: 10.1038/s42004-019-0172-x. Epub 2019 Jul 3. PMID:32382661 doi:http://dx.doi.org/10.1038/s42004-019-0172-x
|
