Crystal structure of human RIOK2 bound to a specific inhibitor.
Open Biol
; 9(4): 190037, 2019 04 26.
Article
em En
| MEDLINE
| ID: mdl-30991936
ABSTRACT
The RIO kinases (RIOKs) are a universal family of atypical kinases that are essential for assembly of the pre-40S ribosome complex. Here, we present the crystal structure of human RIO kinase 2 (RIOK2) bound to a specific inhibitor. This first crystal structure of an inhibitor-bound RIO kinase reveals the binding mode of the inhibitor and explains the structure-activity relationship of the inhibitor series. The inhibitor binds in the ATP-binding site and forms extensive hydrophobic interactions with residues at the entrance to the ATP-binding site. Analysis of the conservation of active site residues reveals the reasons for the specificity of the inhibitor for RIOK2 over RIOK1 and RIOK3, and it provides a template for inhibitor design against the human RIOK family.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Conformação Proteica
/
Proteínas Serina-Treonina Quinases
/
Domínio Catalítico
/
Inibidores de Proteínas Quinases
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article