Structural insights for producing CK2α1-specific inhibitors.
Binding mode
CK2α1
Conformational change
Crystal structure
Selectivity
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
15 01 2020
15 01 2020
Historique:
received:
02
10
2019
revised:
06
11
2019
accepted:
15
11
2019
pubmed:
21
12
2019
medline:
17
2
2021
entrez:
21
12
2019
Statut:
ppublish
Résumé
Casein kinase 2 catalytic subunit (CK2α) is classified into two subtypes CK2α1 and CK2α2. CK2α1 is a drug discovery target, whereas CK2α2 is an off-target of CK2α1 inhibitors. High amino acid sequence homology between these subtypes hampers efforts to produce ATP competitive inhibitors that are highly selective to CK2α1. Hematein was identified previously as a non-ATP-competitive inhibitor for CK2α1, whereas this compound acts as an ATP competitive CK2α2 inhibitor. Crystal structures of CK2α1 and CK2α2 in complex with hematein revealed distinct binding features that provide structural insights for producing CK2α1-selective inhibitors.
Identifiants
pubmed: 31859160
pii: S0960-894X(19)30809-1
doi: 10.1016/j.bmcl.2019.126837
pii:
doi:
Substances chimiques
CSNK2A1 protein, human
EC 2.7.11.1
Casein Kinase II
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
126837Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.