Structural Aspects of LIMK Regulation and Pharmacology.
Cells
; 11(1)2022 01 02.
Article
em En
| MEDLINE
| ID: mdl-35011704
ABSTRACT
Malfunction of the actin cytoskeleton is linked to numerous human diseases including neurological disorders and cancer. LIMK1 (LIM domain kinase 1) and its paralogue LIMK2 are two closely related kinases that control actin cytoskeleton dynamics. Consequently, they are potential therapeutic targets for the treatment of such diseases. In the present review, we describe the LIMK conformational space and its dependence on ligand binding. Furthermore, we explain the unique catalytic mechanism of the kinase, shedding light on substrate recognition and how LIMK activity is regulated. The structural features are evaluated for implications on the drug discovery process. Finally, potential future directions for targeting LIMKs pharmacologically, also beyond just inhibiting the kinase domain, are discussed.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosforilação
/
Actinas
/
Fatores de Despolimerização de Actina
/
Quinases Lim
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article