Identification of the New Covalent Allosteric Binding Site of Fructose-1,6-bisphosphatase with Disulfiram Derivatives toward Glucose Reduction.
Allosteric Site
Animals
Binding Sites
Blood Glucose
/ analysis
Crystallography, X-Ray
Diabetes Mellitus, Experimental
/ drug therapy
Disulfiram
/ analogs & derivatives
Drug Design
Fructose-Bisphosphatase
/ antagonists & inhibitors
Humans
Hydrogen Bonding
Kinetics
Mice
Mice, Inbred ICR
Mice, Obese
Molecular Dynamics Simulation
Mutagenesis, Site-Directed
Protein Conformation, alpha-Helical
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
11 06 2020
11 06 2020
Historique:
pubmed:
8
5
2020
medline:
13
11
2020
entrez:
8
5
2020
Statut:
ppublish
Résumé
Fructose 1,6-bisphosphatase (FBPase) has attracted substantial interest as a target associated with cancer and type 2 diabetes. Herein, we found that disulfiram and its derivatives can potently inhibit FBPase by covalently binding to a new C128 allosteric site distinct from the original C128 site in APO FBPase. Further identification of the allosteric inhibition mechanism reveals that the covalent binding of a fragment of
Identifiants
pubmed: 32375478
doi: 10.1021/acs.jmedchem.0c00699
doi:
Substances chimiques
Blood Glucose
0
Fructose-Bisphosphatase
EC 3.1.3.11
Disulfiram
TR3MLJ1UAI
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM