View source for 9ydm


==Targeting PTPN22 at non-orthosteric binding sites - a fragment approach==
<StructureSection load='9ydm' size='340' side='right'caption='[[9ydm]], [[Resolution|resolution]] 1.99&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ydm]] 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=9YDM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9YDM 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]] 1.99&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1CU3:N-(3-methyl-1H-pyrazol-5-yl)-3-phenylpropanamide'>A1CU3</scene>, <scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=9ydm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ydm OCA], [https://pdbe.org/9ydm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ydm RCSB], [https://www.ebi.ac.uk/pdbsum/9ydm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ydm ProSAT]</span></td></tr>
</table>
== Disease ==
[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> 
== Function ==
[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> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Di Lello P]]
[[Category: Wells MM]]