Year: 2019
Type: article
Abstract: ) 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: Communications Chemistry
Language: English
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,170
Funders: U.S. Department of Energy, U.S. Department of Health and Human Services, National Institutes of Health, Office of Science, National Institute on Aging, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, Office of Research Infrastructure Programs, National Institutes of Health, Argonne National Laboratory
Awards: G102163711, G107546177, G1313983767, G1664757510, G1739031488, Targeting CD44-mediated calcium signaling for the treatment of relapsed myeloma, G2164036156, G2287611682, G254657075, G262962599, G3075337988, Pixel Array Detector for X-ray Crystallography, G3407338877, G409777406, G498139845, G5201631574, West Virginia University Stroke COBRE, G5607048534, G5711190109, G5915780612, G615728318, G666778509, G6848031779, G6918803902, miRNA Regulation of the Mitochondrial Genome, G7263181930, G7949020550, G8114618634, G818230603, Development of mitoNEET agonists for the treatment of stroke, NE-CAT Center for Advanced Macromolecular Crystallography, G8952802627, G8989615353, G9000087594, G9000112972, G9000119994, G9000133327, G921583954, G969889393, G993149817
OpenAlex ID: W2954431205