5vr6
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Structure of Human Sts-1 histidine phosphatase domain with sulfate bound== | |
| + | <StructureSection load='5vr6' size='340' side='right' caption='[[5vr6]], [[Resolution|resolution]] 1.87Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5vr6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VR6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VR6 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5vr6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vr6 OCA], [http://pdbe.org/5vr6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vr6 RCSB], [http://www.ebi.ac.uk/pdbsum/5vr6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vr6 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/UBS3B_HUMAN UBS3B_HUMAN]] Interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases. Promotes accumulation of activated target receptors, such as T-cell receptors and EGFR, on the cell surface. Exhibits tyrosine phosphatase activity toward several substrates including EGFR, FAK, SYK, and ZAP70. Down-regulates proteins that are dually modified by both protein tyrosine phosphorylation and ubiquitination.<ref>PMID:15159412</ref> <ref>PMID:17880946</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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, C. albicans. This suggests that modulation of the host immune response by inhibiting Sts function may be a viable strategy to treat 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 solved the X-ray crystal structures of Sts-1HP, unliganded and in complex with sulfate to 2.5 A and 1.9 A, respectively, and the structure of Sts-2HP with sulfate to 2.4 A. The steady-state kinetic analysis shows, as expected, that Sts-1HP has a significantly higher phosphatase activity 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 identified that the SHP-1 inhibitor, PHPS1, is a potent inhibitor of Sts-1 (Ki of 1.05 +/- 0.15 microM). 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 provides a structural basis for future drug development efforts. | ||
| - | + | Structural and functional characterization of the histidine phosphatase domains of human Sts-1 and Sts-2.,Zhou W, Yin Y, Weinheimer AS, Kaur N, Carpino N, French JB Biochemistry. 2017 Jul 31. doi: 10.1021/acs.biochem.7b00638. PMID:28759203<ref>PMID:28759203</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 5vr6" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Protein-tyrosine-phosphatase]] | ||
[[Category: Carpino, N]] | [[Category: Carpino, N]] | ||
| - | [[Category: | + | [[Category: French, J B]] |
| + | [[Category: Kaur, N]] | ||
| + | [[Category: Weinheimer, A W]] | ||
[[Category: Yin, Y]] | [[Category: Yin, Y]] | ||
| - | [[Category: | + | [[Category: Zhou, W]] |
| - | [[Category: | + | [[Category: Histidine phosphatase]] |
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Protein tyrosine phosphatase]] | ||
| + | [[Category: T-cell receptor]] | ||
| + | [[Category: Zap-70]] | ||
Revision as of 05:53, 17 August 2017
Structure of Human Sts-1 histidine phosphatase domain with sulfate bound
| |||||||||||
