[摘要]：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. SERPINA3-1 (uniprotkb: Q9TTE1) binds tighly to human CASP3 ( uniprotkb: P42574) and CASP8 ( uniprotkb: Q14790) with kass of 4.2 x 10(5) and 1.4 x 10(6) M (1) s (1), respectively. A wholly similar inhibition of human CASP3 and CASP8 by SERPINA3-3 ( uniprotkb: Q3ZEJ6) was also observed with k(ass) of 1.5 x 10(5) and 2.7 x 10(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. Structured summary: MINT-7234656: CASP8 ( uniprotkb: Q14790) and SERPINA3-1 (uniprotkb: Q9TTE1) bind (MI: 0407) by biochemical ( MI: 0401) MINT-7234634: SERPINA3-3 ( uniprotkb: Q3ZEJ6) and CASP3 (uniprotkb: P42574) bind (MI: 0407) by biochemical ( MI: 0401) MINT-7234663: CASP8 ( uniprotkb: Q14790) and SERPINA3- 3 (uniprotkb: Q3ZEJ6) bind (MI: 0407) by biochemical ( MI: 0401) MINT-7234625: SERPINA3- 1 (uniprotkb: Q9TTE1) and CASP3 (uniprotkb: P42574) bind (MI: 0407) by biochemical ( MI: 0401) (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
