Structure and inhibition analysis of the mouse SAD-B C-terminal fragment.
Biosci Biotechnol Biochem
; 80(10): 1939-46, 2016 Oct.
Article
em En
| MEDLINE
| ID: mdl-27251228
ABSTRACT
The SAD (synapses of amphids defective) kinases, including SAD-A and SAD-B, play important roles in the regulation of neuronal development, cell cycle, and energy metabolism. Our recent study of mouse SAD-A identified a unique autoinhibitory sequence (AIS), which binds at the junction of the kinase domain (KD) and the ubiquitin-associated (UBA) domain and exerts autoregulation in cooperation with UBA. Here, we report the crystal structure of the mouse SAD-B C-terminal fragment including the AIS and the kinase-associated domain 1 (KA1) at 2.8 Å resolution. The KA1 domain is structurally conserved, while the isolated AIS sequence is highly flexible and solvent-accessible. Our biochemical studies indicated that the SAD-B AIS exerts the same autoinhibitory role as that in SAD-A. We believe that the flexible isolated AIS sequence is readily available for interaction with KD-UBA and thus inhibits SAD-B activity.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Proteínas Serina-Treonina Quinases
Limite:
Animals
Idioma:
En
Revista:
Biosci Biotechnol Biochem
Assunto da revista:
BIOQUIMICA
/
BIOTECNOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China