3v5l: Difference between revisions

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-{{STRUCTURE_3v5l|  PDB=3v5l  |  SCENE=  }}
-===Crystal Structure of Interleukin-2 Inducible T-cell Kinase Itk Catalytic Domain with Thienopyrazolylindole Inhibitor 542===
-{{ABSTRACT_PUBMED_22464456}}
-==Disease==
+==Crystal Structure of Interleukin-2 Inducible T-cell Kinase Itk Catalytic Domain with Thienopyrazolylindole Inhibitor 542==
-[[http://www.uniprot.org/uniprot/ITK_HUMAN ITK_HUMAN]] Defects in ITK are the cause of lymphoproliferative syndrome EBV-associated autosomal type 1 (LPSA1) [MIM:[http://omim.org/entry/613011 613011]]. LPSA1 is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Inadequate immune response to EBV can have a fatal outcome. Clinical features include splenomegaly, lymphadenopathy, anemia, thrombocytopenia, pancytopenia, recurrent infections. There is an increased risk for lymphoma.<ref>PMID:19425169</ref>
+<StructureSection load='3v5l' size='340' side='right'caption='[[3v5l]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3v5l]] is a 4 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=3V5L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V5L 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]] 1.86&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G1:3-[3-(4-METHOXYPHENYL)-2-(1H-THIENO[3,2-C]PYRAZOL-3-YL)-1H-INDOL-6-YL]PENTAN-3-OL'>0G1</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=3v5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v5l OCA], [https://pdbe.org/3v5l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v5l RCSB], [https://www.ebi.ac.uk/pdbsum/3v5l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v5l ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/ITK_HUMAN ITK_HUMAN] Defects in ITK are the cause of lymphoproliferative syndrome EBV-associated autosomal type 1 (LPSA1) [MIM:[https://omim.org/entry/613011 613011]. LPSA1 is a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Inadequate immune response to EBV can have a fatal outcome. Clinical features include splenomegaly, lymphadenopathy, anemia, thrombocytopenia, pancytopenia, recurrent infections. There is an increased risk for lymphoma.<ref>PMID:19425169</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/ITK_HUMAN ITK_HUMAN] Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation.<ref>PMID:12186560</ref> <ref>PMID:12682224</ref> <ref>PMID:21725281</ref>
-==Function==
+==See Also==
-[[http://www.uniprot.org/uniprot/ITK_HUMAN ITK_HUMAN]] Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation.<ref>PMID:12186560</ref><ref>PMID:12682224</ref><ref>PMID:21725281</ref>
+*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
+== References ==
-==About this Structure==
+<references/>
-[[3v5l]] is a 4 chain structure with 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=3V5L OCA].
+__TOC__
+</StructureSection>
-==Reference==
-<ref group="xtra">PMID:022464456</ref><references group="xtra"/><references/>
 [[Category: Homo sapiens]]
-[[Category: Non-specific protein-tyrosine kinase]]
+[[Category: Large Structures]]
-[[Category: McLean, L R.]]
+[[Category: McLean LR]]
-[[Category: Zhang, Y.]]
+[[Category: Zhang Y]]
-[[Category: Kinase]]
-[[Category: Transferase-transferase inhibitor complex]]