7P0O

mitoNEET bound to M1 molecule

Summary for 7P0O

• Entry DOI: 10.2210/pdb7p0o/pdb
• Descriptor: CDGSH iron-sulfur domain-containing protein 1, FE2/S2 (INORGANIC) CLUSTER, 2-benzamido-4-[(2~{R})-1,2,3,4-tetrahydronaphthalen-2-yl]thiophene-3-carboxylic acid, ... (5 entities in total)
• Functional Keywords: [2fe-2s] proteins, neet proteins, destabilizer, m1, metal binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 19003.21

Authors

Livnah, O.,Eisenberg-Domovich, Y.,Marjault, H.B.,Nechushtai, R. (deposition date: 2021-06-30, release date: 2022-05-25, Last modification date: 2024-01-31)

Primary citation

Marjault, H.B.,Karmi, O.,Zuo, K.,Michaeli, D.,Eisenberg-Domovich, Y.,Rossetti, G.,de Chassey, B.,Vonderscher, J.,Cabantchik, I.,Carloni, P.,Mittler, R.,Livnah, O.,Meldrum, E.,Nechushtai, R.
An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters.
Commun Biol, 5:437-437, 2022

PubMed Abstract: Elevated levels of mitochondrial iron and reactive oxygen species (ROS) accompany the progression of diabetes, negatively impacting insulin production and secretion from pancreatic cells. In search for a tool to reduce mitochondrial iron and ROS levels, we arrived at a molecule that destabilizes the [2Fe-2S] clusters of NEET proteins (M1). Treatment of db/db diabetic mice with M1 improved hyperglycemia, without the weight gain observed with alternative treatments such as rosiglitazone. The molecular interactions of M1 with the NEET proteins mNT and NAF-1 were determined by X-crystallography. The possibility of controlling diabetes by molecules that destabilize the [2Fe-2S] clusters of NEET proteins, thereby reducing iron-mediated oxidative stress, opens a new route for managing metabolic aberration such as in diabetes.

PubMed: 35538231
DOI: 10.1038/s42003-022-03393-x

Experimental method

X-RAY DIFFRACTION (1.65 Å)