Search Menu
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information
Search Scholarly Publications

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

Journal Article · · Communications Chemistry
 [1];  [2];  [1]; ORCiD logo [3];  [1];  [1]; ORCiD logo [4];  [5];  [1];  [1];  [6]; ORCiD logo [1]
  1. West Virginia Univ., Morgantown, WV (United States)
  2. Marshall Univ., Huntington, WV (United States)
  3. Nippon Medical School, Sendagi, Tokyo (Japan)
  4. Ball State Univ., Muncie, IN (United States)
  5. Univ. of Louisville, KY (United States)
  6. West Virginia Univ., Morgantown, WV (United States); Modulation Therapeutics, Morgantown, WV (United States)
+ Show Author Affiliations

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
National Institutes of Health (NIH); National Institute of General Medical Sciences (NIGMS); Office of Research Infrastructure Programs (ORIP); USDOE Office of Science (SC); Ohio Valley Whipkey Trust
Grant/Contract Number:
S10 RR029205; AC02-06CH11357
OSTI ID:
1557303
Journal Information:
Communications Chemistry, Vol. 2, Issue 1; ISSN 2399-3669
Publisher:
Springer NatureCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

References (29)

The H 2 O 2 -Resistant Fe–S Redox Switch MitoNEET Acts as a pH Sensor To Repair Stress-Damaged Fe–S Protein journal August 2018
Crystal Structure of Miner1: The Redox-active 2Fe-2S Protein Causative in Wolfram Syndrome 2 journal September 2009
Redox Characterization of the FeS Protein MitoNEET and Impact of Thiazolidinedione Drug Binding journal November 2009
Anamorsin/Ndor1 Complex Reduces [2Fe–2S]-MitoNEET via a Transient Protein–Protein Interaction journal July 2017
MitoNEET (CISD1) Knockout Mice Show Signs of Striatal Mitochondrial Dysfunction and a Parkinson’s Disease Phenotype journal September 2017
MitoNEET-Parkin Effects in Pancreatic α- and β-Cells, Cellular Survival, and Intrainsular Cross Talk journal February 2016
Structure-based design of a thiazolidinedione which targets the mitochondrial protein mitoNEET journal February 2010
Features and development of Coot journal March 2010
Mutation of the His ligand in mitoNEET stabilizes the 2Fe–2S cluster despite conformational heterogeneity in the ligand environment journal May 2011
MitoNEET Protects HL-1 Cardiomyocytes from Oxidative Stress Mediated Apoptosis in an In Vitro Model of Hypoxia and Reoxygenation journal May 2016
Quantitative Proteomics of Presynaptic Mitochondria Reveal an Overexpression and Biological Relevance of Neuronal MitoNEET in Postnatal Brain Development journal April 2019
Maternal-engineered nanomaterial exposure disrupts progeny cardiac function and bioenergetics journal March 2017
Mitochondrial Dysfunction in Parkinson’s Disease: New Mechanistic Insights and Therapeutic Perspectives journal April 2018
mitoNEET as a novel drug target for mitochondrial dysfunction journal October 2014
MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone journal August 2007
Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress journal March 2015
An Aggregation Advisor for Ligand Discovery journal August 2015
The Fe-S cluster-containing NEET proteins mitoNEET and NAF-1 as chemotherapeutic targets in breast cancer journal March 2015
The unique fold and lability of the [2Fe-2S] clusters of NEET proteins mediate their key functions in health and disease journal February 2018
MitoNEET-driven alterations in adipocyte mitochondrial activity reveal a crucial adaptive process that preserves insulin sensitivity in obesity journal September 2012
Complexes of the Outer Mitochondrial Membrane Protein MitoNEET with Resveratrol-3-Sulfate journal June 2011
NEET Proteins: A New Link Between Iron Metabolism, Reactive Oxygen Species, and Cancer journal March 2019
Dense quasicrystalline tilings by squares and equilateral triangles journal December 2009
Redox Control of the Human Iron-Sulfur Repair Protein MitoNEET Activity via Its Iron-Sulfur Cluster journal February 2016
Identification of a novel mitochondrial protein (“mitoNEET”) cross-linked specifically by a thiazolidinedione photoprobe journal February 2004
Arachidonic acid interaction with the mitochondrial electron transport chain promotes reactive oxygen species generation journal July 1999
Identification of small molecules that bind to the mitochondrial protein mitoNEET journal November 2016
Structure of the human monomeric NEET protein MiNT and its role in regulating iron and reactive oxygen species in cancer cells journal December 2017
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome journal December 2019

Similar Records

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Drug discovery
Structural biology