3h2x

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{{Seed}}
 
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[[Image:3h2x.png|left|200px]]
 
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==Crystal Structure of The Human Lymphoid Tyrosine Phosphatase Catalytic Domain==
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The line below this paragraph, containing "STRUCTURE_3h2x", creates the "Structure Box" on the page.
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<StructureSection load='3h2x' size='340' side='right'caption='[[3h2x]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3h2x]] 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=3H2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3H2X FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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{{STRUCTURE_3h2x| PDB=3h2x | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3h2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h2x OCA], [https://pdbe.org/3h2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3h2x RCSB], [https://www.ebi.ac.uk/pdbsum/3h2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3h2x ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/PTN22_HUMAN PTN22_HUMAN] Defects in PTPN22 are a cause of susceptibility to systemic lupus erythematosus (SLE) [MIM:[https://omim.org/entry/152700 152700]. SLE is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system.<ref>PMID:15273934</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/PTN22_HUMAN PTN22_HUMAN] Acts as negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules. Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue. Dephosphorylates ZAP70 at its activating 'Tyr-493' residue. Dephosphorylates the immune system activator SKAP2.<ref>PMID:16461343</ref> <ref>PMID:18056643</ref> <ref>PMID:19167335</ref> <ref>PMID:21719704</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h2/3h2x_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=3h2x ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene, recently emerged as an important risk factor and drug target for human autoimmunity. Here we solved the structure of the catalytic domain of LYP, which revealed noticeable differences with previously published structures. The active center with a semi-closed conformation binds a phosphate ion, which may represent an intermediate conformation after dephosphorylation of the substrate but before release of the phosphate product. The structure also revealed an unusual disulfide bond formed between the catalytic Cys and one of the two Cys residues nearby, which is not observed in previously determined structures. Our structural and mutagenesis data suggest that the disulfide bond may play a role in protecting the enzyme from irreversible oxidation. Surprisingly, we found that the two noncatalytic Cys around the active center exert an opposite yin-yang regulation on the catalytic Cys activity. These detailed structural and functional characterizations have provided new insights into autoregulatory mechanisms of LYP function.
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===Crystal Structure of The Human Lymphoid Tyrosine Phosphatase Catalytic Domain===
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Crystal structure of the human lymphoid tyrosine phosphatase catalytic domain: insights into redox regulation .,Tsai SJ, Sen U, Zhao L, Greenleaf WB, Dasgupta J, Fiorillo E, Orru V, Bottini N, Chen XS Biochemistry. 2009 Jun 9;48(22):4838-45. PMID:19371084<ref>PMID:19371084</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3h2x" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_19371084}}, adds the Publication Abstract to the page
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*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 19371084 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_19371084}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3H2X is a 1 chain 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=3H2X OCA].
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==Reference==
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<ref group="xtra">PMID:19371084</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein-tyrosine-phosphatase]]
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[[Category: Large Structures]]
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[[Category: Sen, U.]]
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[[Category: Sen U]]
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[[Category: Tsai, S J.]]
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[[Category: Tsai SJ]]
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[[Category: Alternative splicing]]
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[[Category: Cytoplasm]]
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[[Category: Hydrolase]]
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[[Category: Polymorphism]]
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[[Category: Protein phosphatase]]
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[[Category: Sh2-like fold]]
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[[Category: Systemic lupus erythematosus]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 8 12:56:31 2009''
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Current revision

Crystal Structure of The Human Lymphoid Tyrosine Phosphatase Catalytic Domain

PDB ID 3h2x

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