|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6d3f' size='340' side='right'caption='[[6d3f]], [[Resolution|resolution]] 2.27Å' scene=''> | | <StructureSection load='6d3f' size='340' side='right'caption='[[6d3f]], [[Resolution|resolution]] 2.27Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6d3f]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D3F OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6D3F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6d3f]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D3F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D3F FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.271Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6d3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3f OCA], [http://pdbe.org/6d3f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d3f RCSB], [http://www.ebi.ac.uk/pdbsum/6d3f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3f ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6d3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3f OCA], [https://pdbe.org/6d3f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d3f RCSB], [https://www.ebi.ac.uk/pdbsum/6d3f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3f ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PTPRE_HUMAN PTPRE_HUMAN]] Isoform 1 plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells. May play a role in osteoclast formation and function (By similarity). Isoform 2 acts as a negative regulator of insulin receptor (IR) signaling in skeletal muscle. Regulates insulin-induced tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate 1 (IRS-1), phosphorylation of protein kinase B and glycogen synthase kinase-3 and insulin induced stimulation of glucose uptake (By similarity). Isoform 1 and isoform 2 act as a negative regulator of FceRI-mediated signal transduction leading to cytokine production and degranulation, most likely by acting at the level of SYK to affect downstream events such as phosphorylation of SLP76 and LAT and mobilization of Ca(2+). | + | [https://www.uniprot.org/uniprot/PTPRE_HUMAN PTPRE_HUMAN] Isoform 1 plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells. May play a role in osteoclast formation and function (By similarity). Isoform 2 acts as a negative regulator of insulin receptor (IR) signaling in skeletal muscle. Regulates insulin-induced tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate 1 (IRS-1), phosphorylation of protein kinase B and glycogen synthase kinase-3 and insulin induced stimulation of glucose uptake (By similarity). Isoform 1 and isoform 2 act as a negative regulator of FceRI-mediated signal transduction leading to cytokine production and degranulation, most likely by acting at the level of SYK to affect downstream events such as phosphorylation of SLP76 and LAT and mobilization of Ca(2+). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 25: |
Line 25: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Protein-tyrosine-phosphatase]]
| + | [[Category: Austin BP]] |
| - | [[Category: Austin, B P]] | + | [[Category: Burke Jr TR]] |
| - | [[Category: Burke, T R]] | + | [[Category: Dyas BK]] |
| - | [[Category: Dyas, B K]] | + | [[Category: Lountos GT]] |
| - | [[Category: Lountos, G T]] | + | [[Category: Raran-Kurussi S]] |
| - | [[Category: Raran-Kurussi, S]] | + | [[Category: Ulrich RG]] |
| - | [[Category: Ulrich, R G]] | + | [[Category: Waugh DS]] |
| - | [[Category: Waugh, D S]] | + | [[Category: Zhao BM]] |
| - | [[Category: Zhao, B M]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Phosphatase]]
| + | |
| Structural highlights
Function
PTPRE_HUMAN Isoform 1 plays a critical role in signaling transduction pathways and phosphoprotein network topology in red blood cells. May play a role in osteoclast formation and function (By similarity). Isoform 2 acts as a negative regulator of insulin receptor (IR) signaling in skeletal muscle. Regulates insulin-induced tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate 1 (IRS-1), phosphorylation of protein kinase B and glycogen synthase kinase-3 and insulin induced stimulation of glucose uptake (By similarity). Isoform 1 and isoform 2 act as a negative regulator of FceRI-mediated signal transduction leading to cytokine production and degranulation, most likely by acting at the level of SYK to affect downstream events such as phosphorylation of SLP76 and LAT and mobilization of Ca(2+).
Publication Abstract from PubMed
Here, new crystal structures are presented of the isolated membrane-proximal D1 and distal D2 domains of protein tyrosine phosphatase epsilon (PTP), a protein tyrosine phosphatase that has been shown to play a positive role in the survival of human breast cancer cells. A triple mutant of the PTP D2 domain (A455N/V457Y/E597D) was also constructed to reconstitute the residues of the PTP D1 catalytic domain that are important for phosphatase activity, resulting in only a slight increase in the phosphatase activity compared with the native D2 protein. The structures reported here are of sufficient resolution for structure-based drug design, and a microarray-based assay for high-throughput screening to identify small-molecule inhibitors of the PTP D1 domain is also described.
High-resolution crystal structures of the D1 and D2 domains of protein tyrosine phosphatase epsilon for structure-based drug design.,Lountos GT, Raran-Kurussi S, Zhao BM, Dyas BK, Burke TR Jr, Ulrich RG, Waugh DS Acta Crystallogr D Struct Biol. 2018 Oct 1;74(Pt 10):1015-1026. doi:, 10.1107/S2059798318011919. Epub 2018 Oct 2. PMID:30289412[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lountos GT, Raran-Kurussi S, Zhao BM, Dyas BK, Burke TR Jr, Ulrich RG, Waugh DS. High-resolution crystal structures of the D1 and D2 domains of protein tyrosine phosphatase epsilon for structure-based drug design. Acta Crystallogr D Struct Biol. 2018 Oct 1;74(Pt 10):1015-1026. doi:, 10.1107/S2059798318011919. Epub 2018 Oct 2. PMID:30289412 doi:http://dx.doi.org/10.1107/S2059798318011919
|
