Crystal structure of a Legionella pneumophila ecto -triphosphate diphosphohydrolase, a structural and functional homolog of the eukaryotic NTPDases.
Structure
; 18(2): 228-38, 2010 Feb 10.
Article
en En
| MEDLINE
| ID: mdl-20159467
ABSTRACT
Many pathogenic bacteria have sophisticated mechanisms to interfere with the mammalian immune response. These include the disruption of host extracellular ATP levels that, in humans, is tightly regulated by the nucleoside triphosphate diphosphohydrolase family (NTPDases). NTPDases are found almost exclusively in eukaryotes, the notable exception being their presence in some pathogenic prokaryotes. To address the function of bacterial NTPDases, we describe the structures of an NTPDase from the pathogen Legionella pneumophila (Lpg1905/Lp1NTPDase) in its apo state and in complex with the ATP analog AMPPNP and the subtype-specific NTPDase inhibitor ARL 67156. Lp1NTPDase is structurally and catalytically related to eukaryotic NTPDases and the structure provides a basis for NTPDase-specific inhibition. Furthermore, we demonstrate that the activity of Lp1NTPDase correlates directly with intracellular replication of Legionella within macrophages. Collectively, these findings provide insight into the mechanism of this enzyme and highlight its role in host-pathogen interactions.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Pirofosfatasas
/
Proteínas Bacterianas
/
Legionella pneumophila
/
Estructura Terciaria de Proteína
/
Eucariontes
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Structure
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
BIOTECNOLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Australia