| http://purl.uniprot.org/citations/28759203 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28759203 | http://www.w3.org/2000/01/rdf-schema#comment | "The suppressor of T cell signaling (Sts) proteins, Sts-1 and Sts-2, are homologous phosphatases that negatively regulate signaling pathways downstream of the T cell receptor. Functional inactivation of Sts-1 and Sts-2 in a murine model leads to resistance to systemic infection by the opportunistic pathogen, Candida albicans. This suggests that modulation of the host immune response by inhibiting Sts function may be a viable strategy for treating these deadly fungal pathogen infections. To better understand the molecular determinants of function and structure, we characterized the structure and steady-state kinetics of the histidine phosphatase domains of human Sts-1 (Sts-1HP) and Sts-2 (Sts-2HP). We determined the X-ray crystal structures of unliganded Sts-1HP and Sts-1HP in complex with sulfate to 2.5 and 1.9 Å, respectively, and the structure of Sts-2HP with sulfate to 2.4 Å. The steady-state kinetic analysis shows, as expected, that Sts-1HP has a phosphatase activity significantly higher than that of Sts-2HP and that the human and mouse proteins behave similarly. In addition, comparison of the phosphatase activity of full-length Sts-1 protein to Sts-1HP reveals similar kinetics, indicating that Sts-1HP is a functional surrogate for the native protein. We also tested known phosphatase inhibitors and determined that the SHP-1 inhibitor, PHPS1, is a potent inhibitor of Sts-1 (Ki = 1.05 ± 0.15 μM). Finally, we demonstrated that human Sts-1 has robust phosphatase activity against the substrate, Zap-70, in a cell-based assay. Collectively, these data suggest that the human Sts proteins are druggable targets and provide a structural basis for future drug development efforts."xsd:string |
| http://purl.uniprot.org/citations/28759203 | http://purl.org/dc/terms/identifier | "doi:10.1021/acs.biochem.7b00638"xsd:string |
| http://purl.uniprot.org/citations/28759203 | http://purl.uniprot.org/core/author | "Zhou W."xsd:string |
| http://purl.uniprot.org/citations/28759203 | http://purl.uniprot.org/core/author | "Yin Y."xsd:string |
| http://purl.uniprot.org/citations/28759203 | http://purl.uniprot.org/core/author | "Kaur N."xsd:string |
| http://purl.uniprot.org/citations/28759203 | http://purl.uniprot.org/core/author | "French J.B."xsd:string |
| http://purl.uniprot.org/citations/28759203 | http://purl.uniprot.org/core/author | "Carpino N."xsd:string |
| http://purl.uniprot.org/citations/28759203 | http://purl.uniprot.org/core/author | "Weinheimer A.S."xsd:string |
| http://purl.uniprot.org/citations/28759203 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28759203 | http://purl.uniprot.org/core/name | "Biochemistry"xsd:string |
| http://purl.uniprot.org/citations/28759203 | http://purl.uniprot.org/core/pages | "4637-4645"xsd:string |
| http://purl.uniprot.org/citations/28759203 | http://purl.uniprot.org/core/title | "Structural and Functional Characterization of the Histidine Phosphatase Domains of Human Sts-1 and Sts-2."xsd:string |
| http://purl.uniprot.org/citations/28759203 | http://purl.uniprot.org/core/volume | "56"xsd:string |
| http://purl.uniprot.org/citations/28759203 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28759203 |
| http://purl.uniprot.org/citations/28759203 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28759203 |
| http://purl.uniprot.org/uniprot/#_P57075-mappedCitation-28759203 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28759203 |
| http://purl.uniprot.org/uniprot/#_Q8TF42-mappedCitation-28759203 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28759203 |
| http://purl.uniprot.org/uniprot/P57075 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/28759203 |
| http://purl.uniprot.org/uniprot/Q8TF42 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/28759203 |