Activity-based probes that target functional subclasses of phospholipases in proteomes.
J Am Chem Soc
; 132(10): 3264-5, 2010 Mar 17.
Article
em En
| MEDLINE
| ID: mdl-20178358
ABSTRACT
Phospholipases are a large and diverse set of enzymes that metabolize the phospholipid components of cell membranes and function in key lipid-signaling pathways. The molecular characterization of novel phospholipases would benefit from chemical probes that selectively target these enzymes on the basis of their distinct substrate specificities and catalytic properties. Here we present the synthesis and characterization of a set of activity-based protein profiling (ABPP) probes that contain key recognition and reactivity elements for targeting phospholipases of the serine hydrolase superfamily. We show that these probes accurately report on the sn-1 and sn-2 substrate specificities of phospholipases in cell and tissue proteomes, including the sn-1-selective phospholipase DDHD1 and a calcium-dependent transacylase activity implicated in endocannabinoid biosynthesis. We anticipate that these phospholipase-directed ABPP probes will facilitate the discovery of new lipid-metabolizing enzymes and provide valuable insights into their substrate preferences.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfolipases
/
Proteoma
/
Alcinos
/
Organofosfonatos
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article