Alternaria toxins as casein kinase 2 inhibitors and possible consequences for estrogenicity: a hybrid in silico/in vitro study.
Alternaria
/ metabolism
Casein Kinase II
/ antagonists & inhibitors
Cell Line, Tumor
Estrogen Receptor alpha
/ agonists
Estrogen Receptor beta
/ agonists
Humans
Lactones
/ metabolism
Ligands
Molecular Docking Simulation
Mycotoxins
/ metabolism
Protein Binding
Protein Conformation
Protein Kinase Inhibitors
/ metabolism
Structure-Activity Relationship
Alternariol
Altertoxin II
Estrogen receptor
Mycotoxin
Journal
Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
17
01
2020
accepted:
08
04
2020
pubmed:
25
4
2020
medline:
13
7
2021
entrez:
25
4
2020
Statut:
ppublish
Résumé
Emerging mycotoxins produced by Alternaria spp. were previously reported to exert cytotoxic, genotoxic, but also estrogenic effects in human cells. The involved mechanisms are very complex and not fully elucidated yet. Thus, we followed an in silico target fishing approach to extend knowledge on the possible biological targets underlying the activity of alternariol, taken as the signature compound of Alternaria toxins. Combining ligand-based screening and structure-based modeling, the ubiquitous casein kinase 2 (CK2) was identified as a potential target for the compound. This result was validated in a cell-free in vitro CK2 activity assay, where alternariol inhibited CK2 with an IC
Identifiants
pubmed: 32328700
doi: 10.1007/s00204-020-02746-x
pii: 10.1007/s00204-020-02746-x
pmc: PMC7303061
doi:
Substances chimiques
ESR1 protein, human
0
ESR2 protein, human
0
Estrogen Receptor alpha
0
Estrogen Receptor beta
0
Lactones
0
Ligands
0
Mycotoxins
0
Protein Kinase Inhibitors
0
Casein Kinase II
EC 2.7.11.1
alternariol
KN9L4260JW
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2225-2237Références
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