Nucleotide-dependent dynamics of the Dengue NS3 helicase.
Biochim Biophys Acta Proteins Proteom
; 1868(8): 140441, 2020 08.
Article
en En
| MEDLINE
| ID: mdl-32371149
ABSTRACT
Dengue represents a substantial public health burden, particularly in low-resource countries. Non-structural protein 3 (NS3) is a multifunctional protein critical in the virus life cycle and has been identified as a promising anti-viral drug target. Despite recent crystallographic studies of the NS3 helicase domain, only subtle structural nucleotide-dependent differences have been identified, such that its coupled ATPase and helicase activities remain mechanistically unclear. Here we use molecular dynamics simulations to explore the nucleotide-dependent conformational landscape of the Dengue virus NS3 helicase and identify substantial changes in the protein flexibility during the ATP hydrolysis cycle. We relate these changes to the RNA-protein interactions and proposed translocation models for other monomeric helicases. Furthermore, we report a novel open-loop conformation with a likely escape route for Pi after hydrolysis, providing new insight into the conformational changes that underlie the ATPase activity of NS3.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fosfatos
/
Adenosina Trifosfato
/
Proteínas no Estructurales Virales
/
Virus del Dengue
Idioma:
En
Revista:
Biochim Biophys Acta Proteins Proteom
Año:
2020
Tipo del documento:
Article
País de afiliación:
Argentina