3vs2 - Revision history

OCA at 12:34, 8 November 2023

2023-11-08T12:34:40Z

← Older revision		Revision as of 12:34, 8 November 2023
Line 3:		Line 3:
	<StructureSection load='3vs2' size='340' side='right'caption='[[3vs2]], [[Resolution\|resolution]] 2.61Å' scene=''>		<StructureSection load='3vs2' size='340' side='right'caption='[[3vs2]], [[Resolution\|resolution]] 2.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3vs2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VS2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VS2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3vs2]] 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=3VS2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VS2 FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>~~, ~~<scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=VSB:7-~~[~~CIS-4-(4-METHYLPIPERAZIN-1-YL)CYCLOHEXYL~~]~~-5-(4-PHENOXYPHENYL)-7H-PYRROLO[~~2~~,3-D]PYRIMIDIN-4-AMINE'>VSB</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]] 2.609Å</td></tr>
	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=~~PTR~~:~~O-PHOSPHOTYROSINE~~'>~~PTR~~</scene><~~/td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=VSB:7-[CIS-4-(4-METHYLPIPERAZIN-1-YL)CYCLOHEXYL]-5-(4-PHENOXYPHENYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>VSB</scene></td></tr>
	~~<tr id~~='~~related'><td class~~=~~"sblockLbl"><b>[[Related_structure\|Related~~:~~]]</b~~></td><~~td class~~=~~"sblockDat"><div style~~=~~'overflow~~: ~~auto; max~~-~~height: 3em;~~'>~~[[3vry\|3vry]], [[3vrz\|3vrz]], [[3vs0\|3vs0]], [[3vs1\|3vs1]], [[3vs3\|3vs3]], [[3vs4\|3vs4]], [[3vs5\|3vs5]], [[3vs6\|3vs6]], [[3vs7\|3vs7]]~~</~~div~~><~~/td></tr>~~
	~~<tr id~~='~~gene'><td class~~=~~"sblockLbl"><b>~~[~~[Gene\|Gene:~~]~~]</b></td><td class="sblockDat">HCK ([https://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'>[https://en.wikipedia.org/wiki/Non~~-~~specific_protein~~-~~tyrosine_kinase Non~~-~~specific protein~~-~~tyrosine kinase]~~, ~~with EC number [https://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=3vs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vs2 OCA], [https://pdbe.org/3vs2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vs2 RCSB], [https://www.ebi.ac.uk/pdbsum/3vs2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vs2 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=3vs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vs2 OCA], [https://pdbe.org/3vs2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vs2 RCSB], [https://www.ebi.ac.uk/pdbsum/3vs2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vs2 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref> Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref>		[https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN] Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref> Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.<ref>PMID:8132624</ref> <ref>PMID:7535819</ref> <ref>PMID:9406996</ref> <ref>PMID:9407116</ref> <ref>PMID:10092522</ref> <ref>PMID:10779760</ref> <ref>PMID:10973280</ref> <ref>PMID:12411494</ref> <ref>PMID:11741929</ref> <ref>PMID:11904303</ref> <ref>PMID:11896602</ref> <ref>PMID:15010462</ref> <ref>PMID:15952790</ref> <ref>PMID:15998323</ref> <ref>PMID:17535448</ref> <ref>PMID:17310994</ref> <ref>PMID:19114024</ref> <ref>PMID:19903482</ref> <ref>PMID:20452982</ref>		[https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN] Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.<ref>PMID:8132624</ref> <ref>PMID:7535819</ref> <ref>PMID:9406996</ref> <ref>PMID:9407116</ref> <ref>PMID:10092522</ref> <ref>PMID:10779760</ref> <ref>PMID:10973280</ref> <ref>PMID:12411494</ref> <ref>PMID:11741929</ref> <ref>PMID:11904303</ref> <ref>PMID:11896602</ref> <ref>PMID:15010462</ref> <ref>PMID:15952790</ref> <ref>PMID:15998323</ref> <ref>PMID:17535448</ref> <ref>PMID:17310994</ref> <ref>PMID:19114024</ref> <ref>PMID:19903482</ref> <ref>PMID:20452982</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Non-specific protein-tyrosine kinase]]~~		[[Category: Handa N]]
	[[Category: Handa, N]]		[[Category: Kuratani M]]
	[[Category: Kuratani, M]]		[[Category: Niwa H]]
	[[Category: Niwa, H]]		[[Category: Parker JL]]
	[[Category: Parker~~, J L~~]]		[[Category: Tomabechi Y]]
	[[Category: Tomabechi, Y]]		[[Category: Yokoyama S]]
	[[Category: Yokoyama, S]]
	~~[[Category: Src-family]]~~
	~~[[Category: Transferase-transferase inhibitor complex]]~~
	~~[[Category: Tyrosine kinase~~]]

OCA at 19:01, 27 July 2022

2022-07-27T19:01:05Z

← Older revision		Revision as of 19:01, 27 July 2022
Line 1:		Line 1:

	==Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor 7-[cis-4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine==		==Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor 7-[cis-4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine==
	<StructureSection load='3vs2' size='340' side='right' caption='[[3vs2]], [[Resolution\|resolution]] 2.61Å' scene=''>		<StructureSection load='3vs2' size='340' side='right'caption='[[3vs2]], [[Resolution\|resolution]] 2.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3vs2]] 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=3VS2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3VS2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3vs2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VS2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VS2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=VSB:7-[CIS-4-(4-METHYLPIPERAZIN-1-YL)CYCLOHEXYL]-5-(4-PHENOXYPHENYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>VSB</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=VSB:7-[CIS-4-(4-METHYLPIPERAZIN-1-YL)CYCLOHEXYL]-5-(4-PHENOXYPHENYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>VSB</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vry\|3vry]], [[3vrz\|3vrz]], [[3vs0\|3vs0]], [[3vs1\|3vs1]], [[3vs3\|3vs3]], [[3vs4\|3vs4]], [[3vs5\|3vs5]], [[3vs6\|3vs6]], [[3vs7\|3vs7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3vry\|3vry]], [[3vrz\|3vrz]], [[3vs0\|3vs0]], [[3vs1\|3vs1]], [[3vs3\|3vs3]], [[3vs4\|3vs4]], [[3vs5\|3vs5]], [[3vs6\|3vs6]], [[3vs7\|3vs7]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HCK ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HCK ([https://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'>[https://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [https://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=3vs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vs2 OCA], [~~http~~://pdbe.org/3vs2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3vs2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3vs2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3vs2 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=3vs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vs2 OCA], [https://pdbe.org/3vs2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vs2 RCSB], [https://www.ebi.ac.uk/pdbsum/3vs2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vs2 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref> Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref>		[[https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref> Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref>
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.<ref>PMID:8132624</ref> <ref>PMID:7535819</ref> <ref>PMID:9406996</ref> <ref>PMID:9407116</ref> <ref>PMID:10092522</ref> <ref>PMID:10779760</ref> <ref>PMID:10973280</ref> <ref>PMID:12411494</ref> <ref>PMID:11741929</ref> <ref>PMID:11904303</ref> <ref>PMID:11896602</ref> <ref>PMID:15010462</ref> <ref>PMID:15952790</ref> <ref>PMID:15998323</ref> <ref>PMID:17535448</ref> <ref>PMID:17310994</ref> <ref>PMID:19114024</ref> <ref>PMID:19903482</ref> <ref>PMID:20452982</ref>		[[https://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.<ref>PMID:8132624</ref> <ref>PMID:7535819</ref> <ref>PMID:9406996</ref> <ref>PMID:9407116</ref> <ref>PMID:10092522</ref> <ref>PMID:10779760</ref> <ref>PMID:10973280</ref> <ref>PMID:12411494</ref> <ref>PMID:11741929</ref> <ref>PMID:11904303</ref> <ref>PMID:11896602</ref> <ref>PMID:15010462</ref> <ref>PMID:15952790</ref> <ref>PMID:15998323</ref> <ref>PMID:17535448</ref> <ref>PMID:17310994</ref> <ref>PMID:19114024</ref> <ref>PMID:19903482</ref> <ref>PMID:20452982</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 26:

	==See Also==		==See Also==
	*[[Tyrosine kinase\|Tyrosine kinase]]		*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 32:		Line 32:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Handa, N]]		[[Category: Handa, N]]

OCA at 17:40, 4 August 2016

2016-08-04T17:40:00Z

← Older revision		Revision as of 17:40, 4 August 2016
Line 1:		Line 1:

	==Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor 7-[cis-4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine==		==Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor 7-[cis-4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine==
	<StructureSection load='3vs2' size='340' side='right' caption='[[3vs2]], [[Resolution\|resolution]] 2.61Å' scene=''>		<StructureSection load='3vs2' size='340' side='right' caption='[[3vs2]], [[Resolution\|resolution]] 2.61Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3vs2]] is a 2 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=3VS2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VS2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3vs2]] 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=3VS2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VS2 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=VSB:7-[CIS-4-(4-METHYLPIPERAZIN-1-YL)CYCLOHEXYL]-5-(4-PHENOXYPHENYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>VSB</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=VSB:7-[CIS-4-(4-METHYLPIPERAZIN-1-YL)CYCLOHEXYL]-5-(4-PHENOXYPHENYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>VSB</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vry\|3vry]], [[3vrz\|3vrz]], [[3vs0\|3vs0]], [[3vs1\|3vs1]], [[3vs3\|3vs3]], [[3vs4\|3vs4]], [[3vs5\|3vs5]], [[3vs6\|3vs6]], [[3vs7\|3vs7]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vry\|3vry]], [[3vrz\|3vrz]], [[3vs0\|3vs0]], [[3vs1\|3vs1]], [[3vs3\|3vs3]], [[3vs4\|3vs4]], [[3vs5\|3vs5]], [[3vs6\|3vs6]], [[3vs7\|3vs7]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HCK ([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=3vs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vs2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vs2 RCSB], [http://www.ebi.ac.uk/pdbsum/3vs2 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=3vs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vs2 OCA], [http://pdbe.org/3vs2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vs2 RCSB], [http://www.ebi.ac.uk/pdbsum/3vs2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vs2 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 22:		Line 23:
	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 3vs2" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 29:		Line 31:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Handa, N]]		[[Category: Handa, N]]

OCA at 07:21, 21 December 2014

2014-12-21T07:21:40Z

← Older revision		Revision as of 07:21, 21 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_3vs2\| PDB=3vs2 \| SCENE= }}~~		==Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor 7-[cis-4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine==
	===Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor 7-[cis-4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine===		<StructureSection load='3vs2' size='340' side='right' caption='[[3vs2]], [[Resolution\|resolution]] 2.61Å' scene=''>
	~~{{ABSTRACT_PUBMED_23596204}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[3vs2]] is a 2 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=3VS2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VS2 FirstGlance]. <br>
	==Disease==		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=VSB:7-[CIS-4-(4-METHYLPIPERAZIN-1-YL)CYCLOHEXYL]-5-(4-PHENOXYPHENYL)-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>VSB</scene></td></tr>
			<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3vry\|3vry]], [[3vrz\|3vrz]], [[3vs0\|3vs0]], [[3vs1\|3vs1]], [[3vs3\|3vs3]], [[3vs4\|3vs4]], [[3vs5\|3vs5]], [[3vs6\|3vs6]], [[3vs7\|3vs7]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HCK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3vs2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vs2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vs2 RCSB], [http://www.ebi.ac.uk/pdbsum/3vs2 PDBsum]</span></td></tr>
			</table>
			== Disease ==
	[[http://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref> Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref>		[[http://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref> Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.<ref>PMID:19114024</ref> <ref>PMID:20452982</ref>
			== Function ==
			[[http://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.<ref>PMID:8132624</ref> <ref>PMID:7535819</ref> <ref>PMID:9406996</ref> <ref>PMID:9407116</ref> <ref>PMID:10092522</ref> <ref>PMID:10779760</ref> <ref>PMID:10973280</ref> <ref>PMID:12411494</ref> <ref>PMID:11741929</ref> <ref>PMID:11904303</ref> <ref>PMID:11896602</ref> <ref>PMID:15010462</ref> <ref>PMID:15952790</ref> <ref>PMID:15998323</ref> <ref>PMID:17535448</ref> <ref>PMID:17310994</ref> <ref>PMID:19114024</ref> <ref>PMID:19903482</ref> <ref>PMID:20452982</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Leukemia stem cells (LSCs) that survive conventional chemotherapy are thought to contribute to disease relapse, leading to poor long-term outcomes for patients with acute myeloid leukemia (AML). We previously identified a Src-family kinase (SFK) member, hematopoietic cell kinase (HCK), as a molecular target that is highly differentially expressed in human primary LSCs compared with human normal hematopoietic stem cells (HSCs). We performed a large-scale chemical library screen that integrated a high-throughput enzyme inhibition assay, in silico binding prediction, and crystal structure determination and found a candidate HCK inhibitor, RK-20449, a pyrrolo-pyrimidine derivative with an enzymatic IC50 (half maximal inhibitory concentration) in the subnanomolar range. A crystal structure revealed that RK-20449 bound the activation pocket of HCK. In vivo administration of RK-20449 to nonobese diabetic (NOD)/severe combined immunodeficient (SCID)/IL2rg(null) mice engrafted with highly aggressive therapy-resistant AML significantly reduced human LSC and non-stem AML burden. By eliminating chemotherapy-resistant LSCs, RK-20449 may help to prevent relapse and lead to improved patient outcomes in AML.

	~~==Function==~~		A Pyrrolo-Pyrimidine Derivative Targets Human Primary AML Stem Cells in Vivo.,Saito Y, Yuki H, Kuratani M, Hashizume Y, Takagi S, Honma T, Tanaka A, Shirouzu M, Mikuni J, Handa N, Ogahara I, Sone A, Najima Y, Tomabechi Y, Wakiyama M, Uchida N, Tomizawa-Murasawa M, Kaneko A, Tanaka S, Suzuki N, Kajita H, Aoki Y, Ohara O, Shultz LD, Fukami T, Goto T, Taniguchi S, Yokoyama S, Ishikawa F Sci Transl Med. 2013 Apr 17;5(181):181ra52. doi: 10.1126/scitranslmed.3004387. PMID:23596204<ref>PMID:23596204</ref>
	~~[[http://www.uniprot.org/uniprot/HCK_HUMAN HCK_HUMAN]] Non~~-~~receptor tyrosine-protein kinase found~~ in ~~hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses~~, ~~including neutrophil~~, ~~monocyte~~, ~~macrophage and mast cell functions~~, ~~phagocytosis~~, ~~cell survival and proliferation~~, ~~cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins~~, ~~such as FCGR1A and FCGR2A~~, ~~but also CSF3R~~, ~~PLAUR~~, ~~the receptors for IFNG~~, ~~IL2~~, ~~IL6 and IL8~~, ~~and integrins~~, ~~such as ITGB1 and ITGB2. During the phagocytic process~~, ~~mediates mobilization of secretory lysosomes~~, ~~degranulation~~, ~~and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization~~, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, ~~BCR~~, ~~ELMO1~~, ~~FCGR2A~~, ~~GAB1~~, ~~GAB2~~, ~~RAPGEF1~~, ~~STAT5B~~, ~~TP73~~, ~~VAV1 and WAS~~.~~<ref>PMID~~:~~8132624</ref> <ref>PMID~~:~~7535819<~~/~~ref> <ref>~~PMID:9406996</ref> <ref>PMID:9407116</ref> <ref>PMID:10092522</ref> <ref>PMID:10779760</ref> <ref>PMID:10973280</ref> <ref>PMID:12411494</ref> <ref>PMID:11741929</ref> <ref>PMID:11904303</ref> <ref>PMID:11896602</ref> <ref>PMID:15010462</ref> <ref>PMID:15952790</ref> <ref>PMID:15998323</ref> <ref>PMID:17535448</ref> <ref>PMID:17310994</ref> <ref>PMID:19114024</ref> <ref>PMID:19903482</ref> <ref>PMID:~~20452982~~</ref>

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[3vs2]] is~~ a ~~2 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=3VS2 OCA].~~		</div>

	==~~Reference~~==		==See Also==
	<references ~~group="xtra"~~/><~~references~~/>		*[[Tyrosine kinase\|Tyrosine kinase]]
			== References ==
			<references/>
			__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Handa, N.]]		[[Category: Handa, N]]
	[[Category: Kuratani, M.]]		[[Category: Kuratani, M]]
	[[Category: Niwa, H.]]		[[Category: Niwa, H]]
	[[Category: Parker, J L.]]		[[Category: Parker, J L]]
	[[Category: Tomabechi, Y.]]		[[Category: Tomabechi, Y]]
	[[Category: Yokoyama, S.]]		[[Category: Yokoyama, S]]
	[[Category: Src-family]]		[[Category: Src-family]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]
	[[Category: Tyrosine kinase]]		[[Category: Tyrosine kinase]]

OCA at 07:42, 2 May 2013

2013-05-02T07:42:47Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+{{STRUCTURE_3vs2|  PDB=3vs2  |  SCENE=  }}
-The entry 3vs2 is ON HOLD  until Paper Publication
+==Disease==
-Authors: Kuratani, M., Tomabechi, Y., Niwa, H., Parker, J.L., Handa, N., Yokoyama, S.
+==Function==
-Description:
+==About this Structure==

OCA at 05:35, 13 June 2012

2012-06-13T05:35:53Z

← Older revision		Revision as of 05:35, 13 June 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 3vs2 is ON HOLD		The entry 3vs2 is ON HOLD until Paper Publication

	Authors: Kuratani, M., Tomabechi, Y., Niwa, H., Parker, J.L., Handa, N., Yokoyama, S.		Authors: Kuratani, M., Tomabechi, Y., Niwa, H., Parker, J.L., Handa, N., Yokoyama, S.

	Description:		Description:

OCA at 07:08, 6 June 2012

2012-06-06T07:08:38Z

← Older revision		Revision as of 07:08, 6 June 2012
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	The entry 3vs2 is ON HOLD		The entry 3vs2 is ON HOLD

	Authors: Kuratani, M., Tomabechi, Y., Niwa, H., Parker, J. L., Handa, N., Yokoyama, S.		Authors: Kuratani, M., Tomabechi, Y., Niwa, H., Parker, J.L., Handa, N., Yokoyama, S.

	Description: ~~Crystal structure of HCK complexed with inhibitors~~		Description:

OCA: Protected "3vs2" [edit=sysop:move=sysop]

2012-05-02T18:46:49Z

Protected "3vs2" [edit=sysop:move=sysop]

← Older revision	Revision as of 18:46, 2 May 2012
(No difference)

OCA: New page: '''Unreleased structure''' The entry 3vs2 is ON HOLD Authors: Kuratani, M., Tomabechi, Y., Niwa, H., Parker, J. L., Handa, N., Yokoyama, S. Description: Crystal structure of HCK comple...

2012-05-02T18:46:48Z

New page: '''Unreleased structure''' The entry 3vs2 is ON HOLD Authors: Kuratani, M., Tomabechi, Y., Niwa, H., Parker, J. L., Handa, N., Yokoyama, S. Description: Crystal structure of HCK comple...

New page

'''Unreleased structure'''

The entry 3vs2 is ON HOLD

Authors: Kuratani, M., Tomabechi, Y., Niwa, H., Parker, J. L., Handa, N., Yokoyama, S.

Description: Crystal structure of HCK complexed with inhibitors