Propylselen inhibits cancer cell growth by targeting glutamate dehydrogenase at the NADP
Antineoplastic Agents
/ chemistry
Azoles
/ chemistry
Binding Sites
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Escherichia coli
/ enzymology
Glutamate Dehydrogenase
/ antagonists & inhibitors
Humans
Isoindoles
Molecular Docking Simulation
NADP
/ metabolism
Neoplasms
/ drug therapy
Organoselenium Compounds
/ chemistry
Biomolecular interaction assay
EGCG
Enzyme kinetics
Glutamate dehydrogenase
Inhibitors
Propylselen
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
29 01 2019
29 01 2019
Historique:
received:
11
12
2018
accepted:
15
12
2018
pubmed:
26
12
2018
medline:
9
10
2019
entrez:
26
12
2018
Statut:
ppublish
Résumé
High levels of glutamate dehydrogenase (GDH) activity are associated with hypoglycemia, cancer, and Parkinson's disease. Propylselen was synthesized to investigate its mechanism of GDH inhibition in comparison with Ebselen and Epigallocatechin gallate (EGCG). Because Ebselen was found to crosslink with the peptide (AA299-341) at the active site of E.coli GDH, the Cys, Pro, and Lys residues of the corresponding peptide were mutagenized to Ala residues. Using enzyme kinetics and biomolecular interaction assays, we found that the conserved GDH P320 residue is important for propylselen binding, C321 for Ebselen binding, and K341 for EGCG binding. In addition, these 3 mutations abolished NADP
Identifiants
pubmed: 30583861
pii: S0006-291X(18)32772-4
doi: 10.1016/j.bbrc.2018.12.117
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Azoles
0
Isoindoles
0
Organoselenium Compounds
0
ebselen
40X2P7DPGH
NADP
53-59-8
Glutamate Dehydrogenase
EC 1.4.1.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
262-267Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.