9yg1: Difference between revisions

Latest revision as of 07:56, 11 February 2026

Targeting PTPN22 at non-orthosteric binding sites - a fragment approach

Structural highlights

9yg1 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.97Å
Ligands:	A1CWL, EOH, GOL, MG, SO4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PTN22_HUMAN Defects in PTPN22 are a cause of susceptibility to systemic lupus erythematosus (SLE) [MIM: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.^[1]

Function

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.^[2] ^[3] ^[4] ^[5]

References

↑ Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, Carlton VE, Chang M, Ramos P, Baechler EC, Batliwalla FM, Novitzke J, Williams AH, Gillett C, Rodine P, Graham RR, Ardlie KG, Gaffney PM, Moser KL, Petri M, Begovich AB, Gregersen PK, Behrens TW. Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet. 2004 Sep;75(3):504-7. Epub 2004 Jul 23. PMID:15273934 doi:10.1086/423790
↑ Wu J, Katrekar A, Honigberg LA, Smith AM, Conn MT, Tang J, Jeffery D, Mortara K, Sampang J, Williams SR, Buggy J, Clark JM. Identification of substrates of human protein-tyrosine phosphatase PTPN22. J Biol Chem. 2006 Apr 21;281(16):11002-10. Epub 2006 Feb 6. PMID:16461343 doi:10.1074/jbc.M600498200
↑ Yu X, Sun JP, He Y, Guo X, Liu S, Zhou B, Hudmon A, Zhang ZY. Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19767-72. Epub 2007 Dec 3. PMID:18056643 doi:10.1073/pnas.0706233104
↑ Barr AJ, Ugochukwu E, Lee WH, King ON, Filippakopoulos P, Alfano I, Savitsky P, Burgess-Brown NA, Muller S, Knapp S. Large-scale structural analysis of the classical human protein tyrosine phosphatome. Cell. 2009 Jan 23;136(2):352-63. PMID:19167335 doi:https://dx.doi.org/10.1016/j.cell.2008.11.038
↑ Yu X, Chen M, Zhang S, Yu ZH, Sun JP, Wang L, Liu S, Imasaki T, Takagi Y, Zhang ZY. Substrate Specificity of Lymphoid-specific Tyrosine Phosphatase (Lyp) and Identification of Src Kinase-associated Protein of 55 kDa Homolog (SKAP-HOM) as a Lyp Substrate. J Biol Chem. 2011 Sep 2;286(35):30526-34. Epub 2011 Jun 30. PMID:21719704 doi:10.1074/jbc.M111.254722

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, Carlton VE, Chang M, Ramos P, Baechler EC, Batliwalla FM, Novitzke J, Williams AH, Gillett C, Rodine P, Graham RR, Ardlie KG, Gaffney PM, Moser KL, Petri M, Begovich AB, Gregersen PK, Behrens TW. Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet. 2004 Sep;75(3):504-7. Epub 2004 Jul 23. PMID:15273934 doi:10.1086/423790

[2] Wu J, Katrekar A, Honigberg LA, Smith AM, Conn MT, Tang J, Jeffery D, Mortara K, Sampang J, Williams SR, Buggy J, Clark JM. Identification of substrates of human protein-tyrosine phosphatase PTPN22. J Biol Chem. 2006 Apr 21;281(16):11002-10. Epub 2006 Feb 6. PMID:16461343 doi:10.1074/jbc.M600498200

[3] Yu X, Sun JP, He Y, Guo X, Liu S, Zhou B, Hudmon A, Zhang ZY. Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19767-72. Epub 2007 Dec 3. PMID:18056643 doi:10.1073/pnas.0706233104

[4] Barr AJ, Ugochukwu E, Lee WH, King ON, Filippakopoulos P, Alfano I, Savitsky P, Burgess-Brown NA, Muller S, Knapp S. Large-scale structural analysis of the classical human protein tyrosine phosphatome. Cell. 2009 Jan 23;136(2):352-63. PMID:19167335 doi:https://dx.doi.org/10.1016/j.cell.2008.11.038

[5] Yu X, Chen M, Zhang S, Yu ZH, Sun JP, Wang L, Liu S, Imasaki T, Takagi Y, Zhang ZY. Substrate Specificity of Lymphoid-specific Tyrosine Phosphatase (Lyp) and Identification of Src Kinase-associated Protein of 55 kDa Homolog (SKAP-HOM) as a Lyp Substrate. J Biol Chem. 2011 Sep 2;286(35):30526-34. Epub 2011 Jun 30. PMID:21719704 doi:10.1074/jbc.M111.254722

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@@ Line 5: / Line 5: @@
 <table><tr><td colspan='2'>[[9yg1]] 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=9YG1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9YG1 FirstGlance]. <br>
 </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.97&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1CWL:1-phenyl-1H-pyrazol-4-ol'>A1CWL</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1CWL:1-phenylpyrazol-4-ol'>A1CWL</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=9yg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9yg1 OCA], [https://pdbe.org/9yg1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9yg1 RCSB], [https://www.ebi.ac.uk/pdbsum/9yg1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9yg1 ProSAT]</span></td></tr>
 </table>

9yg1: Difference between revisions

Latest revision as of 07:56, 11 February 2026

Targeting PTPN22 at non-orthosteric binding sites - a fragment approach

Structural highlights

Disease

Function

References

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