6DE9

mitoNEET bound to furosemide

Summary for 6DE9

• Entry DOI: 10.2210/pdb6de9/pdb
• Descriptor: CDGSH iron-sulfur domain-containing protein 1, FE2/S2 (INORGANIC) CLUSTER, 5-(AMINOSULFONYL)-4-CHLORO-2-[(2-FURYLMETHYL)AMINO]BENZOIC ACID, ... (4 entities in total)
• Functional Keywords: mitoneet, fes, furosemide, metal binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 9685.17

Authors

Robart, A.R.,Geldenhuys, W.J. (deposition date: 2018-05-11, release date: 2019-05-15, Last modification date: 2023-10-11)

Primary citation

Geldenhuys, W.J.,Long, T.E.,Saralkar, P.,Iwasaki, T.,Nunez, R.A.A.,Nair, R.R.,Konkle, M.E.,Menze, M.A.,Pinti, M.V.,Hollander, J.M.,Hazlehurst, L.A.,Robart, A.R.
Crystal structure of the mitochondrial protein mitoNEET bound to a benze-sulfonide ligand.
Commun Chem, 2:-, 2019

PubMed Abstract: MitoNEET (gene ) 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.

PubMed: 32382661
DOI: 10.1038/s42004-019-0172-x

Experimental method

X-RAY DIFFRACTION (1.95 Å)