4qd6 - Revision history

OCA at 12:45, 1 March 2024

OCA — Fri, 01 Mar 2024 12:45:27 GMT

←Older revision		Revision as of 12:45, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4qd6]] 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=4QD6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QD6 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4qd6]] 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=4QD6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QD6 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=30T:TRANS-4-({6-[(5-PHENYL-1H-PYRAZOL-3-YL)AMINO]-4-(PHENYLSULFONYL)PYRIDIN-2-YL}AMINO)CYCLOHEXANOL'>30T</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]] 2.45Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=30T:TRANS-4-({6-[(5-PHENYL-1H-PYRAZOL-3-YL)AMINO]-4-(PHENYLSULFONYL)PYRIDIN-2-YL}AMINO)CYCLOHEXANOL'>30T</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=4qd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qd6 OCA], [https://pdbe.org/4qd6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qd6 RCSB], [https://www.ebi.ac.uk/pdbsum/4qd6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qd6 ProSAT]</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=4qd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qd6 OCA], [https://pdbe.org/4qd6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qd6 RCSB], [https://www.ebi.ac.uk/pdbsum/4qd6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qd6 ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== Function ==		== 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>		[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>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Starting from benzylpyrimidine 2, molecular modeling and X-ray crystallography were used to design highly potent inhibitors of Interleukin-2 inducible T-cell kinase (ITK). Sulfonylpyridine 4i showed sub-nanomolar affinity against ITK, was selective versus Lck and its activity in the Jurkat cell-based assay was greatly improved over 2.
-
-	Design, synthesis and structure-activity relationships of a novel class of sulfonylpyridine inhibitors of Interleukin-2 inducible T-cell kinase (ITK).,Trani G, Barker JJ, Bromidge SM, Brookfield FA, Burch JD, Chen Y, Eigenbrot C, Heifetz A, Ismaili MH, Johnson A, Krulle TM, MacKinnon CH, Maghames R, McEwan PA, Montalbetti CA, Ortwine DF, Perez-Fuertes Y, Vaidya DG, Wang X, Zarrin AA, Pei Z Bioorg Med Chem Lett. 2014 Dec 15;24(24):5818-23. doi:, 10.1016/j.bmcl.2014.10.020. Epub 2014 Oct 12. PMID:25455497<ref>PMID:25455497</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4qd6" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 11:23, 15 February 2023

OCA — Wed, 15 Feb 2023 11:23:45 GMT

←Older revision		Revision as of 11:23, 15 February 2023
Line 3:		Line 3:
	<StructureSection load='4qd6' size='340' side='right'caption='[[4qd6]], [[Resolution\|resolution]] 2.45Å' scene=''>		<StructureSection load='4qd6' size='340' side='right'caption='[[4qd6]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qd6]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QD6 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4QD6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qd6]] 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=4QD6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QD6 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=30T:TRANS-4-({6-[(5-PHENYL-1H-PYRAZOL-3-YL)AMINO]-4-(PHENYLSULFONYL)PYRIDIN-2-YL}AMINO)CYCLOHEXANOL'>30T</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=30T:TRANS-4-({6-[(5-PHENYL-1H-PYRAZOL-3-YL)AMINO]-4-(PHENYLSULFONYL)PYRIDIN-2-YL}AMINO)CYCLOHEXANOL'>30T</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4mf0\|4mf0]], [[4mf1\|4mf1]]</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=4qd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qd6 OCA], [https://pdbe.org/4qd6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qd6 RCSB], [https://www.ebi.ac.uk/pdbsum/4qd6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qd6 ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ITK, EMT, LYK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4qd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qd6 OCA], [~~http~~://pdbe.org/4qd6 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4qd6 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4qd6 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4qd6 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 22:

	==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: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific protein-tyrosine kinase]]~~	+	[[Category: Barker JJ]]
-	[[Category: Barker~~, J J~~]]	+	[[Category: Eigenbrot C]]
-	[[Category: Eigenbrot, C]]	+	[[Category: McEwan PA]]
-	[[Category: McEwan~~, P A]]~~	+
-	~~[[Category: Phosphotransfer catalyst]]~~	+
-	~~[[Category: Protein kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 08:51, 24 April 2019

OCA — Wed, 24 Apr 2019 08:51:15 GMT

←Older revision		Revision as of 08:51, 24 April 2019
Line 1:		Line 1:

	==ITK kinase domain in complex with inhibitor compound==		==ITK kinase domain in complex with inhibitor compound==
-	<StructureSection load='4qd6' size='340' side='right' caption='[[4qd6]], [[Resolution\|resolution]] 2.45Å' scene=''>	+	<StructureSection load='4qd6' size='340' side='right'caption='[[4qd6]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4qd6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QD6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QD6 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4qd6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QD6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QD6 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=30T:TRANS-4-({6-[(5-PHENYL-1H-PYRAZOL-3-YL)AMINO]-4-(PHENYLSULFONYL)PYRIDIN-2-YL}AMINO)CYCLOHEXANOL'>30T</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=30T:TRANS-4-({6-[(5-PHENYL-1H-PYRAZOL-3-YL)AMINO]-4-(PHENYLSULFONYL)PYRIDIN-2-YL}AMINO)CYCLOHEXANOL'>30T</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4mf0\|4mf0]], [[4mf1\|4mf1]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4mf0\|4mf0]], [[4mf1\|4mf1]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ITK, EMT, LYK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qd6 OCA], [http://pdbe.org/4qd6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qd6 RCSB], [http://www.ebi.ac.uk/pdbsum/4qd6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qd6 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=4qd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qd6 OCA], [http://pdbe.org/4qd6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qd6 RCSB], [http://www.ebi.ac.uk/pdbsum/4qd6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qd6 ProSAT]</span></td></tr>
Line 29:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Barker, J J]]		[[Category: Barker, J J]]

OCA at 10:00, 11 August 2016

OCA — Thu, 11 Aug 2016 10:00:35 GMT

←Older revision		Revision as of 10:00, 11 August 2016
Line 1:		Line 1:
		+
	==ITK kinase domain in complex with inhibitor compound==		==ITK kinase domain in complex with inhibitor compound==
	<StructureSection load='4qd6' size='340' side='right' caption='[[4qd6]], [[Resolution\|resolution]] 2.45Å' scene=''>		<StructureSection load='4qd6' size='340' side='right' caption='[[4qd6]], [[Resolution\|resolution]] 2.45Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4mf0\|4mf0]], [[4mf1\|4mf1]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4mf0\|4mf0]], [[4mf1\|4mf1]]</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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qd6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qd6 RCSB], [http://www.ebi.ac.uk/pdbsum/4qd6 PDBsum]</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=4qd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qd6 OCA], [http://pdbe.org/4qd6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qd6 RCSB], [http://www.ebi.ac.uk/pdbsum/4qd6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qd6 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4qd6" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tyrosine kinase\|Tyrosine kinase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 13:36, 14 January 2015

OCA — Wed, 14 Jan 2015 13:36:03 GMT

←Older revision		Revision as of 13:36, 14 January 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==ITK kinase domain in complex with inhibitor compound==
		+	<StructureSection load='4qd6' size='340' side='right' caption='[[4qd6]], [[Resolution\|resolution]] 2.45Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4qd6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QD6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QD6 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=30T:TRANS-4-({6-[(5-PHENYL-1H-PYRAZOL-3-YL)AMINO]-4-(PHENYLSULFONYL)PYRIDIN-2-YL}AMINO)CYCLOHEXANOL'>30T</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4mf0\|4mf0]], [[4mf1\|4mf1]]</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qd6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qd6 RCSB], [http://www.ebi.ac.uk/pdbsum/4qd6 PDBsum]</span></td></tr>
		+	</table>
		+	== 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>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Starting from benzylpyrimidine 2, molecular modeling and X-ray crystallography were used to design highly potent inhibitors of Interleukin-2 inducible T-cell kinase (ITK). Sulfonylpyridine 4i showed sub-nanomolar affinity against ITK, was selective versus Lck and its activity in the Jurkat cell-based assay was greatly improved over 2.

-	~~The entry 4qd6 is ON HOLD until Paper Publication~~	+	Design, synthesis and structure-activity relationships of a novel class of sulfonylpyridine inhibitors of Interleukin-2 inducible T-cell kinase (ITK).,Trani G, Barker JJ, Bromidge SM, Brookfield FA, Burch JD, Chen Y, Eigenbrot C, Heifetz A, Ismaili MH, Johnson A, Krulle TM, MacKinnon CH, Maghames R, McEwan PA, Montalbetti CA, Ortwine DF, Perez-Fuertes Y, Vaidya DG, Wang X, Zarrin AA, Pei Z Bioorg Med Chem Lett. 2014 Dec 15;24(24):5818-23. doi:, 10.1016/j.bmcl.2014.10.020. Epub 2014 Oct 12. PMID:25455497<ref>PMID:25455497</ref>

-	~~Authors: McEwan~~, P.A.~~, Barker, J.J., Eigenbrot, C~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: ITK kinase domain in complex with inhibitor compound~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
-	[[Category: ~~Mcewan~~, ~~P.A~~]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific protein-tyrosine kinase]]
		+	[[Category: Barker, J J]]
	[[Category: Eigenbrot, C]]		[[Category: Eigenbrot, C]]
-	[[Category: ~~Barker~~, ~~J.J~~]]	+	[[Category: McEwan, P A]]
		+	[[Category: Phosphotransfer catalyst]]
		+	[[Category: Protein kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 15:38, 24 December 2014

OCA — Wed, 24 Dec 2014 15:38:46 GMT

←Older revision		Revision as of 15:38, 24 December 2014
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	Description: ITK kinase domain in complex with inhibitor compound		Description: ITK kinase domain in complex with inhibitor compound
		+	[[Category: Unreleased Structures]]
		+	[[Category: Mcewan, P.A]]
		+	[[Category: Eigenbrot, C]]
		+	[[Category: Barker, J.J]]

OCA at 11:19, 19 November 2014

OCA — Wed, 19 Nov 2014 11:19:16 GMT

←Older revision		Revision as of 11:19, 19 November 2014
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4qd6 is ON HOLD	+	The entry 4qd6 is ON HOLD until Paper Publication

	Authors: McEwan, P.A., Barker, J.J., Eigenbrot, C.		Authors: McEwan, P.A., Barker, J.J., Eigenbrot, C.

	Description: ITK kinase domain in complex with inhibitor compound		Description: ITK kinase domain in complex with inhibitor compound

OCA: Protected "4qd6" [edit=sysop:move=sysop]

OCA — Wed, 21 May 2014 08:18:44 GMT

Protected "4qd6" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:18, 21 May 2014

OCA: New page: '''Unreleased structure''' The entry 4qd6 is ON HOLD Authors: McEwan, P.A., Barker, J.J., Eigenbrot, C. Description: ITK kinase domain in complex with inhibitor compound

OCA — Wed, 21 May 2014 08:18:42 GMT

New page: '''Unreleased structure''' The entry 4qd6 is ON HOLD Authors: McEwan, P.A., Barker, J.J., Eigenbrot, C. Description: ITK kinase domain in complex with inhibitor compound

New page

'''Unreleased structure'''

The entry 4qd6 is ON HOLD

Authors: McEwan, P.A., Barker, J.J., Eigenbrot, C.

Description: ITK kinase domain in complex with inhibitor compound