The dynamic organization of fungal acetyl-CoA carboxylase.
Nat Commun
; 7: 11196, 2016 Apr 13.
Article
en En
| MEDLINE
| ID: mdl-27073141
ABSTRACT
Acetyl-CoA carboxylases (ACCs) catalyse the committed step in fatty-acid biosynthesis:
the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA. They are important regulatory hubs for metabolic control and relevant drug targets for the treatment of the metabolic syndrome and cancer. Eukaryotic ACCs are single-chain multienzymes characterized by a large, non-catalytic central domain (CD), whose role in ACC regulation remains poorly characterized. Here we report the crystal structure of the yeast ACC CD, revealing a unique four-domain organization. A regulatory loop, which is phosphorylated at the key functional phosphorylation site of fungal ACC, wedges into a crevice between two domains of CD. Combining the yeast CD structure with intermediate and low-resolution data of larger fragments up to intact ACCs provides a comprehensive characterization of the dynamic fungal ACC architecture. In contrast to related carboxylases, large-scale conformational changes are required for substrate turnover, and are mediated by the CD under phosphorylation control.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Acetil-CoA Carboxilasa
/
Saccharomyces cerevisiae
/
Proteínas de Saccharomyces cerevisiae
Límite:
Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Suiza