Artículo
Insights into the product release mechanism of dengue virus NS3 helicase
Adler, Natalia Sol
; Cababie, Leila Alejandra
; Sarto, Carolina
; Cavasotto, Claudio Norberto
; Gebhard, Leopoldo German
; Estrin, Dario Ariel
; Gamarnik, Andrea Vanesa
; Arrar, Mehrnoosh
; Kaufman, Sergio Benjamín
Fecha de publicación:
06/2022
Editorial:
Oxford University Press
Revista:
Nucleic Acids Research
ISSN:
0305-1048
e-ISSN:
1362-4962
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The non-structural protein 3 helicase (NS3h) is a multifunctional protein that is critical in RNA replication and other stages in the flavivirus life cycle. NS3h uses energy from ATP hydrolysis to translocate along single stranded nucleic acid and to unwind double stranded RNA. Here we present a detailed mechanistic analysis of the product release stage in the catalytic cycle of the dengue virus (DENV) NS3h. This study is based on a combined experimental and computational approach of product-inhibition studies and free energy calculations. Our results support a model in which the catalytic cycle of ATP hydrolysis proceeds through an ordered sequential mechanism that includes a ternary complex intermediate (NS3h-Pi-ADP), which evolves releasing the first product, phosphate (Pi), and subsequently ADP. Our results indicate that in the product release stage of the DENV NS3h a novel open-loop conformation plays an important role that may be conserved in NS3 proteins of other flaviviruses as well.
Palabras clave:
DENGUE
,
HELICASE
,
PRODUCT RELEASE
,
ATP HYDROLYSIS
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Articulos(CIBION)
Articulos de CENTRO DE INVESTIGACIONES EN BIONANOCIENCIAS "ELIZABETH JARES ERIJMAN"
Articulos de CENTRO DE INVESTIGACIONES EN BIONANOCIENCIAS "ELIZABETH JARES ERIJMAN"
Articulos(IIBBA)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos(IIMT)
Articulos de INSTITUTO DE INVESTIGACIONES EN MEDICINA TRASLACIONAL
Articulos de INSTITUTO DE INVESTIGACIONES EN MEDICINA TRASLACIONAL
Articulos(INQUIMAE)
Articulos de INST.D/QUIM FIS D/L MATERIALES MEDIOAMB Y ENERGIA
Articulos de INST.D/QUIM FIS D/L MATERIALES MEDIOAMB Y ENERGIA
Articulos(IQUIBICEN)
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos de INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CS. EXACTAS Y NATURALES
Articulos(IQUIFIB)
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos(SEDE CENTRAL)
Articulos de SEDE CENTRAL
Articulos de SEDE CENTRAL
Citación
Adler, Natalia Sol; Cababie, Leila Alejandra; Sarto, Carolina; Cavasotto, Claudio Norberto; Gebhard, Leopoldo German; et al.; Insights into the product release mechanism of dengue virus NS3 helicase; Oxford University Press; Nucleic Acids Research; 50; 12; 6-2022; 6968-6979
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