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| - | [[Image:1gfy.jpg|left|200px]] | |
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| - | <!-- | + | ==RESIDUE 259 IS A KEY DETERMINANT OF SUBSTRATE SPECIFICITY OF PROTEIN-TYROSINE PHOSPHATASE 1B AND ALPHA== |
| - | The line below this paragraph, containing "STRUCTURE_1gfy", creates the "Structure Box" on the page.
| + | <StructureSection load='1gfy' size='340' side='right'caption='[[1gfy]], [[Resolution|resolution]] 2.13Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet) | + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1gfy]] is a 1 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=1GFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GFY FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display. | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.13Å</td></tr> |
| - | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COL:2-(OXALYL-AMINO)-4,7-DIHYDRO-5H-THIENO[2,3-C]THIOPYRAN-3-CARBOXYLIC+ACID'>COL</scene></td></tr> |
| - | {{STRUCTURE_1gfy| PDB=1gfy | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1gfy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gfy OCA], [https://pdbe.org/1gfy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gfy RCSB], [https://www.ebi.ac.uk/pdbsum/1gfy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gfy ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PTN1_HUMAN PTN1_HUMAN] Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.<ref>PMID:21135139</ref> <ref>PMID:22169477</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gf/1gfy_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1gfy ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The aim of this study was to define the structural elements that determine the differences in substrate recognition capacity of two protein-tyrosine phosphatases (PTPs), PTP1B and PTPalpha, both suggested to be negative regulators of insulin signaling. Since the Ac-DADE(pY)L-NH(2) peptide is well recognized by PTP1B, but less efficiently by PTPalpha, it was chosen as a tool for these analyses. Calpha regiovariation analyses and primary sequence alignments indicate that residues 47, 48, 258, and 259 (PTP1B numbering) define a selectivity-determining region. By analyzing a set of DADE(pY)L analogs with a series of PTP mutants in which these four residues were exchanged between PTP1B and PTPalpha, either in combination or alone, we here demonstrate that the key selectivity-determining residue is 259. In PTPalpha, this residue is a glutamine causing steric hindrance and in PTP1B a glycine allowing broad substrate recognition. Significantly, replacing Gln(259) with a glycine almost turns PTPalpha into a PTP1B-like enzyme. By using a novel set of PTP inhibitors and x-ray crystallography, we further provide evidence that Gln(259) in PTPalpha plays a dual role leading to restricted substrate recognition (directly via steric hindrance) and reduced catalytic activity (indirectly via Gln(262)). Both effects may indicate that PTPalpha regulates highly selective signal transduction processes. |
| | | | |
| - | '''RESIDUE 259 IS A KEY DETERMINANT OF SUBSTRATE SPECIFICITY OF PROTEIN-TYROSINE PHOSPHATASE 1B AND ALPHA'''
| + | Residue 259 is a key determinant of substrate specificity of protein-tyrosine phosphatases 1B and alpha.,Peters GH, Iversen LF, Branner S, Andersen HS, Mortensen SB, Olsen OH, Moller KB, Moller NP J Biol Chem. 2000 Jun 16;275(24):18201-9. PMID:10748206<ref>PMID:10748206</ref> |
| - | | + | |
| - | | + | |
| - | ==Overview==
| + | |
| - | The aim of this study was to define the structural elements that determine the differences in substrate recognition capacity of two protein-tyrosine phosphatases (PTPs), PTP1B and PTPalpha, both suggested to be negative regulators of insulin signaling. Since the Ac-DADE(pY)L-NH(2) peptide is well recognized by PTP1B, but less efficiently by PTPalpha, it was chosen as a tool for these analyses. Calpha regiovariation analyses and primary sequence alignments indicate that residues 47, 48, 258, and 259 (PTP1B numbering) define a selectivity-determining region. By analyzing a set of DADE(pY)L analogs with a series of PTP mutants in which these four residues were exchanged between PTP1B and PTPalpha, either in combination or alone, we here demonstrate that the key selectivity-determining residue is 259. In PTPalpha, this residue is a glutamine causing steric hindrance and in PTP1B a glycine allowing broad substrate recognition. Significantly, replacing Gln(259) with a glycine almost turns PTPalpha into a PTP1B-like enzyme. By using a novel set of PTP inhibitors and x-ray crystallography, we further provide evidence that Gln(259) in PTPalpha plays a dual role leading to restricted substrate recognition (directly via steric hindrance) and reduced catalytic activity (indirectly via Gln(262)). Both effects may indicate that PTPalpha regulates highly selective signal transduction processes.
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1GFY is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GFY OCA].
| + | </div> |
| | + | <div class="pdbe-citations 1gfy" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | Residue 259 is a key determinant of substrate specificity of protein-tyrosine phosphatases 1B and alpha., Peters GH, Iversen LF, Branner S, Andersen HS, Mortensen SB, Olsen OH, Moller KB, Moller NP, J Biol Chem. 2000 Jun 16;275(24):18201-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10748206 10748206]
| + | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Protein-tyrosine-phosphatase]] | + | [[Category: Large Structures]] |
| - | [[Category: Single protein]]
| + | [[Category: Iversen LF]] |
| - | [[Category: Iversen, L F.]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 17:30:55 2008''
| + | |
| Structural highlights
Function
PTN1_HUMAN Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The aim of this study was to define the structural elements that determine the differences in substrate recognition capacity of two protein-tyrosine phosphatases (PTPs), PTP1B and PTPalpha, both suggested to be negative regulators of insulin signaling. Since the Ac-DADE(pY)L-NH(2) peptide is well recognized by PTP1B, but less efficiently by PTPalpha, it was chosen as a tool for these analyses. Calpha regiovariation analyses and primary sequence alignments indicate that residues 47, 48, 258, and 259 (PTP1B numbering) define a selectivity-determining region. By analyzing a set of DADE(pY)L analogs with a series of PTP mutants in which these four residues were exchanged between PTP1B and PTPalpha, either in combination or alone, we here demonstrate that the key selectivity-determining residue is 259. In PTPalpha, this residue is a glutamine causing steric hindrance and in PTP1B a glycine allowing broad substrate recognition. Significantly, replacing Gln(259) with a glycine almost turns PTPalpha into a PTP1B-like enzyme. By using a novel set of PTP inhibitors and x-ray crystallography, we further provide evidence that Gln(259) in PTPalpha plays a dual role leading to restricted substrate recognition (directly via steric hindrance) and reduced catalytic activity (indirectly via Gln(262)). Both effects may indicate that PTPalpha regulates highly selective signal transduction processes.
Residue 259 is a key determinant of substrate specificity of protein-tyrosine phosphatases 1B and alpha.,Peters GH, Iversen LF, Branner S, Andersen HS, Mortensen SB, Olsen OH, Moller KB, Moller NP J Biol Chem. 2000 Jun 16;275(24):18201-9. PMID:10748206[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nievergall E, Janes PW, Stegmayer C, Vail ME, Haj FG, Teng SW, Neel BG, Bastiaens PI, Lackmann M. PTP1B regulates Eph receptor function and trafficking. J Cell Biol. 2010 Dec 13;191(6):1189-203. doi: 10.1083/jcb.201005035. Epub 2010, Dec 6. PMID:21135139 doi:10.1083/jcb.201005035
- ↑ Krishnan N, Fu C, Pappin DJ, Tonks NK. H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. Sci Signal. 2011 Dec 13;4(203):ra86. doi: 10.1126/scisignal.2002329. PMID:22169477 doi:10.1126/scisignal.2002329
- ↑ Peters GH, Iversen LF, Branner S, Andersen HS, Mortensen SB, Olsen OH, Moller KB, Moller NP. Residue 259 is a key determinant of substrate specificity of protein-tyrosine phosphatases 1B and alpha. J Biol Chem. 2000 Jun 16;275(24):18201-9. PMID:10748206 doi:10.1074/jbc.M910273199
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