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

Publication Type:

Journal Article

Source:

Communications Chemistry, Volume 2, Number 1, p.77 (2019)

ISBN:

2399-3669

Abstract:

<p>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&nbsp; soluble&nbsp; domain of&nbsp; 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&rsquo;s and Parkinson&rsquo;s disease.</p>

PDB: 
6DE9
Detector: 
PILATUS
Beamline: 
24-ID-C