| http://purl.uniprot.org/citations/23269243 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23269243 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23269243 | http://www.w3.org/2000/01/rdf-schema#comment | "The granzyme/perforin pathway is a major mechanism for cytotoxic lymphocytes to eliminate virus-infected and tumor cells. The balance between activation and inhibition of the proteolytic cascade must be tightly controlled to avoid self damage. Granzyme H (GzmH) is constitutively expressed in NK cells and induces target cell death; however, how GzmH activity is regulated remains elusive. We reported earlier the crystal structures of inactive D102N-GzmH alone and in complex with its synthetic substrate and inhibitor, as well as defined the mechanisms of substrate recognition and enzymatic activation. In this study, we identified SERPINB1 as a potent intracellular inhibitor for GzmH. Upon cleavage of the reactive center loop at Phe(343), SERPINB1 forms an SDS-stable covalent complex with GzmH. SERPINB1 overexpression suppresses GzmH- or LAK cell-mediated cytotoxicity. We determined the crystal structures of active GzmH and SERPINB1 (LM-DD mutant) in the native conformation to 3.0- and 2.9-Å resolution, respectively. Molecular modeling reveals the possible conformational changes in GzmH for the suicide inhibition. Our findings provide new insights into the inhibitory mechanism of SERPINB1 against human GzmH."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1202542"xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1202542"xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Liu P."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Liu P."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Liu S."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Liu S."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Li Q."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Li Q."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Fan Z."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Fan Z."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Tong L."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Tong L."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Yang X."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Yang X."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Zhang H."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Zhang H."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Wang L."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Wang L."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Zhu P."xsd:string |
| http://purl.uniprot.org/citations/23269243 | http://purl.uniprot.org/core/author | "Zhu P."xsd:string |