4ppb: Difference between revisions

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==ITK kinase domain with compound 28 (N-{1-[(1S)-3-(DIMETHYLAMINO)-1-PHENYLPROPYL]-1H-PYRAZOL-4-YL}-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE)==
==ITK kinase domain with compound 28 (N-{1-[(1S)-3-(DIMETHYLAMINO)-1-PHENYLPROPYL]-1H-PYRAZOL-4-YL}-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE)==
<StructureSection load='4ppb' size='340' side='right' caption='[[4ppb]], [[Resolution|resolution]] 2.82&Aring;' scene=''>
<StructureSection load='4ppb' size='340' side='right'caption='[[4ppb]], [[Resolution|resolution]] 2.82&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4ppb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PPB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PPB FirstGlance]. <br>
<table><tr><td colspan='2'>[[4ppb]] 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=4PPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PPB FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2VV:N-{1-[(1S)-3-(DIMETHYLAMINO)-1-PHENYLPROPYL]-1H-PYRAZOL-4-YL}-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE'>2VV</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.82&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pp9|4pp9]], [[4ppa|4ppa]], [[4ppc|4ppc]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2VV:N-{1-[(1S)-3-(DIMETHYLAMINO)-1-PHENYLPROPYL]-1H-PYRAZOL-4-YL}-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3-CARBOXAMIDE'>2VV</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></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=4ppb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppb OCA], [https://pdbe.org/4ppb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ppb RCSB], [https://www.ebi.ac.uk/pdbsum/4ppb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppb ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ppb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ppb OCA], [http://pdbe.org/4ppb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ppb RCSB], [http://www.ebi.ac.uk/pdbsum/4ppb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ppb ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[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>
[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 ==
== Function ==
[[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>
[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>  
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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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==See Also==
==See Also==
*[[Tyrosine kinase|Tyrosine kinase]]
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Non-specific protein-tyrosine kinase]]
[[Category: Homo sapiens]]
[[Category: Eigenbrot, C]]
[[Category: Large Structures]]
[[Category: Shia, S]]
[[Category: Eigenbrot C]]
[[Category: Protein kinase]]
[[Category: Shia S]]
[[Category: Transferase-transferase inhibitor complex]]

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