5nkc - Revision history

OCA at 13:02, 15 November 2023

2023-11-15T13:02:45Z

←Older revision		Revision as of 13:02, 15 November 2023
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	<StructureSection load='5nkc' size='340' side='right'caption='[[5nkc]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='5nkc' size='340' side='right'caption='[[5nkc]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nkc]] is a 1 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=5NKC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5NKC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nkc]] is a 1 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=5NKC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NKC FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=90T:(3~{S})-1-[3-[[5-[(2-chloranyl-6-methyl-phenyl)carbamoyl]-1,3-thiazol-2-yl]amino]phenyl]carbonylpyrrolidine-3-carboxylic+acid'>90T</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.448Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EPHA2, ECK ([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=90T:(3~{S})-1-[3-[[5-[(2-chloranyl-6-methyl-phenyl)carbamoyl]-1,3-thiazol-2-yl]amino]phenyl]carbonylpyrrolidine-3-carboxylic+acid'>90T</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5nkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nkc OCA], [https://pdbe.org/5nkc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nkc RCSB], [https://www.ebi.ac.uk/pdbsum/5nkc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nkc 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=5nkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nkc OCA], [~~http~~://pdbe.org/5nkc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5nkc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5nkc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5nkc ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/EPHA2_HUMAN EPHA2_HUMAN]] Genetic variations in EPHA2 are the cause of susceptibility to cataract cortical age-related type 2 (ARCC2) [MIM:[~~http~~://omim.org/entry/613020 613020]]. A developmental punctate opacity common in the cortex and present in most lenses. The cataract is white or cerulean, increases in number with age, but rarely affects vision.<ref>PMID:19573808</ref> <ref>PMID:19649315</ref> Defects in EPHA2 are the cause of cataract posterior polar type 1 (CTPP1) [MIM:[~~http~~://omim.org/entry/116600 116600]]. A subcapsular opacity, usually disk-shaped, located at the back of the lens. It can have a marked effect on visual acuity.<ref>PMID:19573808</ref> <ref>PMID:19005574</ref> <ref>PMID:19306328</ref> <ref>PMID:22570727</ref> Note=Overexpressed in several cancer types and promotes malignancy.<ref>PMID:19573808</ref>	+	[https://www.uniprot.org/uniprot/EPHA2_HUMAN EPHA2_HUMAN] Genetic variations in EPHA2 are the cause of susceptibility to cataract cortical age-related type 2 (ARCC2) [MIM:[https://omim.org/entry/613020 613020]. A developmental punctate opacity common in the cortex and present in most lenses. The cataract is white or cerulean, increases in number with age, but rarely affects vision.<ref>PMID:19573808</ref> <ref>PMID:19649315</ref> Defects in EPHA2 are the cause of cataract posterior polar type 1 (CTPP1) [MIM:[https://omim.org/entry/116600 116600]. A subcapsular opacity, usually disk-shaped, located at the back of the lens. It can have a marked effect on visual acuity.<ref>PMID:19573808</ref> <ref>PMID:19005574</ref> <ref>PMID:19306328</ref> <ref>PMID:22570727</ref> Note=Overexpressed in several cancer types and promotes malignancy.<ref>PMID:19573808</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/EPHA2_HUMAN EPHA2_HUMAN]] Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.<ref>PMID:10655584</ref> <ref>PMID:16236711</ref> <ref>PMID:18339848</ref> <ref>PMID:19573808</ref> <ref>PMID:20679435</ref> <ref>PMID:20861311</ref>	+	[https://www.uniprot.org/uniprot/EPHA2_HUMAN EPHA2_HUMAN] Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.<ref>PMID:10655584</ref> <ref>PMID:16236711</ref> <ref>PMID:18339848</ref> <ref>PMID:19573808</ref> <ref>PMID:20679435</ref> <ref>PMID:20861311</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 29:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein-tyrosine kinase]]~~	+	[[Category: Gande SL]]
-	[[Category: Gande~~, S L~~]]	+	[[Category: Heinzlmeir S]]
-	[[Category: Heinzlmeir, S]]	+	[[Category: Kudlinzki D]]
-	[[Category: Kudlinzki, D]]	+	[[Category: Kuester B]]
-	[[Category: Kuester, B]]	+	[[Category: Linhard VL]]
-	[[Category: Linhard~~, V L~~]]	+	[[Category: Medard G]]
-	[[Category: Medard, G]]	+	[[Category: Saxena K]]
-	[[Category: Saxena, K]]	+	[[Category: Schwalbe H]]
-	[[Category: Schwalbe, H]]	+	[[Category: Witt K]]
-	[[Category: Witt, K]]	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Protein tyrosine kinase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 17:12, 14 August 2019

2019-08-14T17:12:21Z

←Older revision		Revision as of 17:12, 14 August 2019
Line 1:		Line 1:

	==Crystal Structure of Ephrin A2 (EphA2) Receptor Protein Kinase with Compound 2h==		==Crystal Structure of Ephrin A2 (EphA2) Receptor Protein Kinase with Compound 2h==
-	<StructureSection load='5nkc' size='340' side='right' caption='[[5nkc]], [[Resolution\|resolution]] 1.45Å' scene=''>	+	<StructureSection load='5nkc' size='340' side='right'caption='[[5nkc]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5nkc]] is a 1 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=5NKC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NKC FirstGlance]. <br>		<table><tr><td colspan='2'>[[5nkc]] is a 1 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=5NKC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NKC FirstGlance]. <br>
Line 22:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5nkc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5nkc" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Ephrin receptor 3D structures\|Ephrin receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 30:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Gande, S L]]		[[Category: Gande, S L]]

OCA at 08:23, 2 May 2018

2018-05-02T08:23:39Z

←Older revision		Revision as of 08:23, 2 May 2018
Line 3:		Line 3:
	<StructureSection load='5nkc' size='340' side='right' caption='[[5nkc]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='5nkc' size='340' side='right' caption='[[5nkc]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nkc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NKC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NKC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nkc]] is a 1 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=5NKC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NKC FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=90T:(3~{S})-1-[3-[[5-[(2-chloranyl-6-methyl-phenyl)carbamoyl]-1,3-thiazol-2-yl]amino]phenyl]carbonylpyrrolidine-3-carboxylic+acid'>90T</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=90T:(3~{S})-1-[3-[[5-[(2-chloranyl-6-methyl-phenyl)carbamoyl]-1,3-thiazol-2-yl]amino]phenyl]carbonylpyrrolidine-3-carboxylic+acid'>90T</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EPHA2, ECK ([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='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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5nkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nkc OCA], [http://pdbe.org/5nkc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nkc RCSB], [http://www.ebi.ac.uk/pdbsum/5nkc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nkc 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=5nkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nkc OCA], [http://pdbe.org/5nkc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nkc RCSB], [http://www.ebi.ac.uk/pdbsum/5nkc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nkc ProSAT]</span></td></tr>
Line 25:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: ~~GANDE~~, S L]]	+	[[Category: Gande, S L]]
-	[[Category: ~~HEINZLMEIR~~, S]]	+	[[Category: Heinzlmeir, S]]
-	[[Category: ~~KUDLINZKI~~, D]]	+	[[Category: Kudlinzki, D]]
-	[[Category: ~~KUESTER~~, B]]	+	[[Category: Kuester, B]]
-	[[Category: ~~LINHARD~~, V L]]	+	[[Category: Linhard, V L]]
-	[[Category: ~~MEDARD~~, G]]	+	[[Category: Medard, G]]
-	[[Category: ~~SAXENA~~, K]]	+	[[Category: Saxena, K]]
-	[[Category: ~~SCHWALBE~~, H]]	+	[[Category: Schwalbe, H]]
-	[[Category: ~~WITT~~, K]]	+	[[Category: Witt, K]]
	[[Category: Complex]]		[[Category: Complex]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]
	[[Category: Protein tyrosine kinase]]		[[Category: Protein tyrosine kinase]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 10:19, 3 August 2017

2017-08-03T10:19:17Z

←Older revision		Revision as of 10:19, 3 August 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The entry ~~5nkc~~ is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal Structure of Ephrin A2 (EphA2) Receptor Protein Kinase with Compound 2h==
		+	<StructureSection load='5nkc' size='340' side='right' caption='[[5nkc]], [[Resolution\|resolution]] 1.45Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5nkc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NKC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NKC FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=90T:(3~{S})-1-[3-[[5-[(2-chloranyl-6-methyl-phenyl)carbamoyl]-1,3-thiazol-2-yl]amino]phenyl]carbonylpyrrolidine-3-carboxylic+acid'>90T</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5nkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nkc OCA], [http://pdbe.org/5nkc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nkc RCSB], [http://www.ebi.ac.uk/pdbsum/5nkc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nkc ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/EPHA2_HUMAN EPHA2_HUMAN]] Genetic variations in EPHA2 are the cause of susceptibility to cataract cortical age-related type 2 (ARCC2) [MIM:[http://omim.org/entry/613020 613020]]. A developmental punctate opacity common in the cortex and present in most lenses. The cataract is white or cerulean, increases in number with age, but rarely affects vision.<ref>PMID:19573808</ref> <ref>PMID:19649315</ref> Defects in EPHA2 are the cause of cataract posterior polar type 1 (CTPP1) [MIM:[http://omim.org/entry/116600 116600]]. A subcapsular opacity, usually disk-shaped, located at the back of the lens. It can have a marked effect on visual acuity.<ref>PMID:19573808</ref> <ref>PMID:19005574</ref> <ref>PMID:19306328</ref> <ref>PMID:22570727</ref> Note=Overexpressed in several cancer types and promotes malignancy.<ref>PMID:19573808</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/EPHA2_HUMAN EPHA2_HUMAN]] Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.<ref>PMID:10655584</ref> <ref>PMID:16236711</ref> <ref>PMID:18339848</ref> <ref>PMID:19573808</ref> <ref>PMID:20679435</ref> <ref>PMID:20861311</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The receptor tyrosine kinase EPHA2 has gained attention as a therapeutic drug target for cancer and infectious diseases. However, EPHA2 research and EPHA2-based therapies have been hampered by the lack of selective small-molecule inhibitors. Herein we report the synthesis and evaluation of dedicated EPHA2 inhibitors based on the clinical BCR-ABL/SRC inhibitor dasatinib as a lead structure. We designed hybrid structures of dasatinib and the previously known EPHA2 binders CHEMBL249097, PD-173955, and a known EPHB4 inhibitor in order to exploit both the ATP pocket entrance as well as the ribose pocket as binding epitopes in the kinase EPHA2. Medicinal chemistry and inhibitor design were guided by a chemical proteomics approach, allowing early selectivity profiling of the newly synthesized inhibitor candidates. Concomitant protein crystallography of 17 inhibitor co-crystals delivered detailed insight into the atomic interactions that underlie the structure-affinity relationship. Finally, the anti-proliferative effect of the inhibitor candidates was confirmed in the glioblastoma cell line SF-268. In this work, we thus discovered a novel EPHA2 inhibitor candidate that features an improved selectivity profile while maintaining potency against EPHA2 and anticancer activity in SF-268 cells.

-	~~Authors: KUDLINZKI, D~~., ~~LINHARD~~, ~~V.L.~~, ~~WITT~~, K., ~~GANDE~~, S~~.L., SAXENA~~, K., ~~HEINZLMEIR~~, S., ~~MEDARD~~, G.~~, KUESTER, B~~., ~~SCHWALBE, H~~.	+	Chemoproteomics-Aided Medicinal Chemistry for the Discovery of EPHA2 Inhibitors.,Heinzlmeir S, Lohse J, Treiber T, Kudlinzki D, Linhard V, Gande SL, Sreeramulu S, Saxena K, Liu X, Wilhelm M, Schwalbe H, Kuster B, Medard G ChemMedChem. 2017 Jun 21;12(12):999-1011. doi: 10.1002/cmdc.201700217. Epub 2017 , Jun 12. PMID:28544567<ref>PMID:28544567</ref>

-	~~Description: Crystal Structure~~ of ~~Ephrin A2 (EphA2) Receptor Protein Kinase with Compound 2h~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Linhard~~, V.L]]	+	<div class="pdbe-citations 5nkc" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Kudlinzki~~, D]]	+	== References ==
-	[[Category: ~~Saxena~~, K]]	+	<references/>
-	[[Category: ~~Witt~~, K]]	+	__TOC__
-	[[Category: ~~Gande~~, S.L]]	+	</StructureSection>
-	[[Category: ~~Medard~~, G]]	+	[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: ~~Schwalbe~~, H]]	+	[[Category: GANDE, S L]]
-	[[Category: ~~Heinzlmeir~~, S]]	+	[[Category: HEINZLMEIR, S]]
-	[[Category: ~~Kuester~~, B]]	+	[[Category: KUDLINZKI, D]]
		+	[[Category: KUESTER, B]]
		+	[[Category: LINHARD, V L]]
		+	[[Category: MEDARD, G]]
		+	[[Category: SAXENA, K]]
		+	[[Category: SCHWALBE, H]]
		+	[[Category: WITT, K]]
		+	[[Category: Complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Protein tyrosine kinase]]
		+	[[Category: Transferase]]

OCA at 09:04, 10 May 2017

2017-05-10T09:04:18Z

←Older revision		Revision as of 09:04, 10 May 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5nkc is ON HOLD	+	The entry 5nkc is ON HOLD until Paper Publication

	Authors: KUDLINZKI, D., LINHARD, V.L., WITT, K., GANDE, S.L., SAXENA, K., HEINZLMEIR, S., MEDARD, G., KUESTER, B., SCHWALBE, H.		Authors: KUDLINZKI, D., LINHARD, V.L., WITT, K., GANDE, S.L., SAXENA, K., HEINZLMEIR, S., MEDARD, G., KUESTER, B., SCHWALBE, H.

OCA: Protected "5nkc" [edit=sysop:move=sysop]

2017-04-05T10:15:24Z

Protected "5nkc" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:15, 5 April 2017

OCA: New page: '''Unreleased structure''' The entry 5nkc is ON HOLD Authors: KUDLINZKI, D., LINHARD, V.L., WITT, K., GANDE, S.L., SAXENA, K., HEINZLMEIR, S., MEDARD, G., KUESTER, B., SCHWALBE, H. Des...

2017-04-05T10:15:23Z

New page: '''Unreleased structure''' The entry 5nkc is ON HOLD Authors: KUDLINZKI, D., LINHARD, V.L., WITT, K., GANDE, S.L., SAXENA, K., HEINZLMEIR, S., MEDARD, G., KUESTER, B., SCHWALBE, H. Des...

New page

'''Unreleased structure'''

The entry 5nkc is ON HOLD

Authors: KUDLINZKI, D., LINHARD, V.L., WITT, K., GANDE, S.L., SAXENA, K., HEINZLMEIR, S., MEDARD, G., KUESTER, B., SCHWALBE, H.

Description: Crystal Structure of Ephrin A2 (EphA2) Receptor Protein Kinase with Compound 2h
[[Category: Unreleased Structures]]
[[Category: Linhard, V.L]]
[[Category: Kudlinzki, D]]
[[Category: Saxena, K]]
[[Category: Witt, K]]
[[Category: Gande, S.L]]
[[Category: Medard, G]]
[[Category: Schwalbe, H]]
[[Category: Heinzlmeir, S]]
[[Category: Kuester, B]]