Inhibition of human initiator caspase 8 and effector caspase 3 by cross-class inhibitory bovSERPINA3-1 and A3-3.
FEBS Lett
; 583(17): 2743-8, 2009 Sep 03.
Article
em En
| MEDLINE
| ID: mdl-19665028
ABSTRACT
Serpins are a superfamily of structurally conserved proteins. Inhibitory serpins use a suicide substrate-like mechanism. Some are able to inhibit cysteine proteases in cross-class inhibition. Here, we demonstrate for the first time the strong inhibition of initiator and effector caspases 3 and 8 by two purified bovine SERPINA3s. SERPINA 3-1 (uniprotkbQ9TTE1) binds tighly to human CASP3 (uniprotkbP42574) and CASP8 (uniprotkbQ14790) with k(ass) of 4.2x10(5) and 1.4x10(6) M(-1)s(-1), respectively. A wholly similar inhibition of human CASP3 and CASP8 by SERPINA3-3 (uniprotkbQ3ZEJ6) was also observed with k(ass) of 1.5x10(5) and 2.7x10(6) M(-1)s(-1), respectively and form SDS-stable complexes with both caspases. By site-directed mutagenesis of bovSERPINA3-3, we identified Asp(371) as the potential P1 residue for caspases. The ability of other members of this family to inhibit trypsin and caspases was analysed and discussed.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Serpinas
/
Isoformas de Proteínas
/
Inibidores de Caspase
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article