7cqe - Revision history

OCA at 16:13, 29 November 2023

2023-11-29T16:13:47Z

←Older revision		Revision as of 16:13, 29 November 2023
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	<StructureSection load='7cqe' size='340' side='right'caption='[[7cqe]], [[Resolution\|resolution]] 2.69Å' scene=''>		<StructureSection load='7cqe' size='340' side='right'caption='[[7cqe]], [[Resolution\|resolution]] 2.69Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7cqe]] 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=7CQE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=7CQE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7cqe]] 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=7CQE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CQE FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>~~, ~~<scene name='pdbligand=YDJ:5-(3-FLUOROPHENYL)-N-~~[~~(3S)-3-PIPERIDYL~~]~~-3-UREIDO-THIOPHENE-~~2~~-CARBOXAMIDE'>YDJ</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]] 2.69Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>MERTK, MER ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</td~~><~~/tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=YDJ:5-(3-FLUOROPHENYL)-N-[(3S)-3-PIPERIDYL]-3-UREIDO-THIOPHENE-2-CARBOXAMIDE'>YDJ</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b~~></td><~~td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[http~~:~~//en.wikipedia.org/wiki/Receptor_protein~~-~~tyrosine_kinase Receptor protein~~-~~tyrosine kinase], with EC number~~ [~~http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=~~2~~.7.10.1 2.7.10.1]~~ </~~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=7cqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cqe OCA], [https://pdbe.org/7cqe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cqe RCSB], [https://www.ebi.ac.uk/pdbsum/7cqe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cqe ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=7cqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cqe OCA], [~~http~~://pdbe.org/7cqe PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=7cqe RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/7cqe PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=7cqe ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/MERTK_HUMAN MERTK_HUMAN]] Defects in MERTK are the cause of retinitis pigmentosa type 38 (RP38) [MIM:[~~http~~://omim.org/entry/613862 613862]]. RP38 is a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.<ref>PMID:11062461</ref>	+	[https://www.uniprot.org/uniprot/MERTK_HUMAN MERTK_HUMAN] Defects in MERTK are the cause of retinitis pigmentosa type 38 (RP38) [MIM:[https://omim.org/entry/613862 613862]. RP38 is a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.<ref>PMID:11062461</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MERTK_HUMAN MERTK_HUMAN]] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.<ref>PMID:17005688</ref>	+	[https://www.uniprot.org/uniprot/MERTK_HUMAN MERTK_HUMAN] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.<ref>PMID:17005688</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: Receptor protein-tyrosine kinase]]~~	+	[[Category: Lee BI]]
-	[[Category: Lee~~, B I~~]]	+	[[Category: Park TH]]
-	[[Category: Park~~, T H]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase inhibitor~~]]	+

OCA at 08:17, 11 November 2020

2020-11-11T08:17:42Z

←Older revision		Revision as of 08:17, 11 November 2020
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	==Crystal structure of the catalytic domain of the proto-oncogene tyrosine-protein kinase MER in complex with AZD-7762==		==Crystal structure of the catalytic domain of the proto-oncogene tyrosine-protein kinase MER in complex with AZD-7762==
-	<StructureSection load='7cqe' size='340' side='right'caption='[[7cqe]]' scene=''>	+	<StructureSection load='7cqe' size='340' side='right'caption='[[7cqe]], [[Resolution\|resolution]] 2.69Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CQE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7CQE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7cqe]] 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=7CQE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7CQE FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7cqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cqe OCA], [http://pdbe.org/7cqe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7cqe RCSB], [http://www.ebi.ac.uk/pdbsum/7cqe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7cqe ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=YDJ:5-(3-FLUOROPHENYL)-N-[(3S)-3-PIPERIDYL]-3-UREIDO-THIOPHENE-2-CARBOXAMIDE'>YDJ</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MERTK, MER ([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/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7cqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cqe OCA], [http://pdbe.org/7cqe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7cqe RCSB], [http://www.ebi.ac.uk/pdbsum/7cqe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7cqe ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/MERTK_HUMAN MERTK_HUMAN]] Defects in MERTK are the cause of retinitis pigmentosa type 38 (RP38) [MIM:[http://omim.org/entry/613862 613862]]. RP38 is a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.<ref>PMID:11062461</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MERTK_HUMAN MERTK_HUMAN]] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.<ref>PMID:17005688</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Aberrant tyrosine-protein kinase Mer (MerTK) expression triggers prosurvival signaling and contributes to cell survival, invasive motility, and chemoresistance in many kinds of cancers. In addition, recent reports suggested that MerTK could be a primary target for abnormal platelet aggregation. Consequently, MerTK inhibitors may promote cancer cell death, sensitize cells to chemotherapy, and act as new antiplatelet agents. We screened an inhouse chemical library to discover novel small-molecule MerTK inhibitors, and identified AZD7762, which is known as a checkpoint-kinase (Chk) inhibitor. The inhibition of MerTK by AZD7762 was validated using an in vitro homogeneous time-resolved fluorescence (HTRF) assay and through monitoring the decrease in phosphorylated MerTK in two lung cancer cell lines. We also determined the crystal structure of the MerTK:AZD7762 complex and revealed the binding mode of AZD7762 to MerTK. Structural information from the MerTK:AZD7762 complex and its comparison with other MerTK:inhibitor structures gave us new insights for optimizing the development of inhibitors targeting MerTK.
		+
		+	Crystal Structure of the Kinase Domain of MerTK in Complex with AZD7762 Provides Clues for Structure-Based Drug Development.,Park TH, Bae SH, Bong SM, Ryu SE, Jang H, Lee BI Int J Mol Sci. 2020 Oct 23;21(21). pii: ijms21217878. doi: 10.3390/ijms21217878. PMID:33114206<ref>PMID:33114206</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7cqe" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Lee BI]]	+	[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: Park TH]]	+	[[Category: Lee, B I]]
		+	[[Category: Park, T H]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase inhibitor]]

OCA at 07:26, 4 November 2020

2020-11-04T07:26:06Z

←Older revision		Revision as of 07:26, 4 November 2020
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-	'''Unreleased structure'''

-	~~The entry 7cqe is ON HOLD until Paper Publication~~	+	==Crystal structure of the catalytic domain of the proto-oncogene tyrosine-protein kinase MER in complex with AZD-7762==
-		+	<StructureSection load='7cqe' size='340' side='right'caption='[[7cqe]]' scene=''>
-	~~Authors: Park, T.H., Lee, B.I.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CQE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7CQE FirstGlance]. <br>
-	~~Description:~~ Crystal structure of the catalytic domain of the proto-oncogene tyrosine-protein kinase MER in complex with AZD-7762	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7cqe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cqe OCA], [http://pdbe.org/7cqe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7cqe RCSB], [http://www.ebi.ac.uk/pdbsum/7cqe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7cqe ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Park~~, T.H]]	+	__TOC__
-	[[Category: Lee~~, B.I~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Lee BI]]
		+	[[Category: Park TH]]

OCA at 18:59, 28 October 2020

2020-10-28T18:59:23Z

←Older revision		Revision as of 18:59, 28 October 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7cqe is ON HOLD	+	The entry 7cqe is ON HOLD until Paper Publication

	Authors: Park, T.H., Lee, B.I.		Authors: Park, T.H., Lee, B.I.

OCA at 06:41, 21 October 2020

2020-10-21T06:41:30Z

←Older revision		Revision as of 06:41, 21 October 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7cqe is ON HOLD ~~until Paper Publication~~	+	The entry 7cqe is ON HOLD

	Authors: Park, T.H., Lee, B.I.		Authors: Park, T.H., Lee, B.I.

OCA at 09:22, 26 August 2020

2020-08-26T09:22:37Z

←Older revision		Revision as of 09:22, 26 August 2020
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7cqe is ON HOLD	+	The entry 7cqe is ON HOLD until Paper Publication

	Authors: Park, T.H., Lee, B.I.		Authors: Park, T.H., Lee, B.I.

OCA: Protected "7cqe" [edit=sysop:move=sysop]

2020-08-19T04:44:29Z

Protected "7cqe" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:44, 19 August 2020

OCA: New page: '''Unreleased structure''' The entry 7cqe is ON HOLD Authors: Park, T.H., Lee, B.I. Description: Crystal structure of the catalytic domain of the proto-oncogene tyrosine-protein kinase...

2020-08-19T04:44:28Z

New page: '''Unreleased structure''' The entry 7cqe is ON HOLD Authors: Park, T.H., Lee, B.I. Description: Crystal structure of the catalytic domain of the proto-oncogene tyrosine-protein kinase...

New page

'''Unreleased structure'''

The entry 7cqe is ON HOLD

Authors: Park, T.H., Lee, B.I.

Description: Crystal structure of the catalytic domain of the proto-oncogene tyrosine-protein kinase MER in complex with AZD-7762
[[Category: Unreleased Structures]]
[[Category: Park, T.H]]
[[Category: Lee, B.I]]