4gk3 - Revision history

OCA at 13:59, 8 November 2023

2023-11-08T13:59:50Z

←Older revision		Revision as of 13:59, 8 November 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4gk3]] 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=4GK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GK3 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4gk3]] 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=4GK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GK3 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L87:8-BUTYL-1-METHYL-7-(2-METHYLPHENYL)-1H-IMIDAZO[2,1-F]PURINE-2,4(3H,8H)-DIONE'>L87</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]] 1.898Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L87:8-BUTYL-1-METHYL-7-(2-METHYLPHENYL)-1H-IMIDAZO[2,1-F]PURINE-2,4(3H,8H)-DIONE'>L87</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=4gk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gk3 OCA], [https://pdbe.org/4gk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gk3 RCSB], [https://www.ebi.ac.uk/pdbsum/4gk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gk3 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=4gk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gk3 OCA], [https://pdbe.org/4gk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gk3 RCSB], [https://www.ebi.ac.uk/pdbsum/4gk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gk3 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:01, 26 October 2022

2022-10-26T07:01:12Z

←Older revision		Revision as of 07:01, 26 October 2022
Line 1:		Line 1:

	==Human EphA3 Kinase domain in complex with ligand 87==		==Human EphA3 Kinase domain in complex with ligand 87==
-	<StructureSection load='4gk3' size='340' side='right' caption='[[4gk3]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='4gk3' size='340' side='right'caption='[[4gk3]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4gk3]] 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=4GK3 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4GK3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4gk3]] 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=4GK3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GK3 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L87:8-BUTYL-1-METHYL-7-(2-METHYLPHENYL)-1H-IMIDAZO[2,1-F]PURINE-2,4(3H,8H)-DIONE'>L87</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L87:8-BUTYL-1-METHYL-7-(2-METHYLPHENYL)-1H-IMIDAZO[2,1-F]PURINE-2,4(3H,8H)-DIONE'>L87</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gk2\|4gk2]], [[4gk4\|4gk4]]</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=4gk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gk3 OCA], [https://pdbe.org/4gk3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gk3 RCSB], [https://www.ebi.ac.uk/pdbsum/4gk3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gk3 ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EphA3 ([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~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4gk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gk3 OCA], [~~http~~://pdbe.org/4gk3 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4gk3 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4gk3 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4gk3 ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/EPHA3_HUMAN EPHA3_HUMAN] Defects in EPHA3 may be a cause of colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500].
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/EPHA3_HUMAN EPHA3_HUMAN] Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin 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. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development.<ref>PMID:11870224</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 22:

	==See Also==		==See Also==
-	*[[Ephrin receptor\|Ephrin receptor]]	+	*[[Ephrin receptor 3D structures\|Ephrin receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Receptor protein-tyrosine kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Caflisch, A]]	+	[[Category: Caflisch A]]
-	[[Category: Dong, J]]	+	[[Category: Dong J]]
-	~~[[Category: Atp-binding]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Receptor tyrosine kinase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 08:45, 11 August 2016

2016-08-11T08:45:05Z

←Older revision		Revision as of 08:45, 11 August 2016
Line 1:		Line 1:
		+
	==Human EphA3 Kinase domain in complex with ligand 87==		==Human EphA3 Kinase domain in complex with ligand 87==
	<StructureSection load='4gk3' size='340' side='right' caption='[[4gk3]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='4gk3' size='340' side='right' caption='[[4gk3]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4gk3]] is a 1 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=4GK3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GK3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4gk3]] 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=4GK3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GK3 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L87:8-BUTYL-1-METHYL-7-(2-METHYLPHENYL)-1H-IMIDAZO[2,1-F]PURINE-2,4(3H,8H)-DIONE'>L87</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L87:8-BUTYL-1-METHYL-7-(2-METHYLPHENYL)-1H-IMIDAZO[2,1-F]PURINE-2,4(3H,8H)-DIONE'>L87</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gk2\|4gk2]], [[4gk4\|4gk4]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gk2\|4gk2]], [[4gk4\|4gk4]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EphA3 ([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">EphA3 ([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=4gk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gk3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gk3 RCSB], [http://www.ebi.ac.uk/pdbsum/4gk3 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=4gk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gk3 OCA], [http://pdbe.org/4gk3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gk3 RCSB], [http://www.ebi.ac.uk/pdbsum/4gk3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gk3 ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 17:		Line 18:
	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 4gk3" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Ephrin receptor\|Ephrin receptor]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Caflisch, A]]		[[Category: Caflisch, A]]

OCA at 14:19, 4 January 2015

2015-01-04T14:19:20Z

←Older revision		Revision as of 14:19, 4 January 2015
Line 1:		Line 1:
-	[[~~Image:~~4gk3.~~jpg~~\|~~left~~\|~~200px~~]]	+	==Human EphA3 Kinase domain in complex with ligand 87==
		+	<StructureSection load='4gk3' size='340' side='right' caption='[[4gk3]], [[Resolution\|resolution]] 1.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4gk3]] is a 1 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=4GK3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GK3 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L87:8-BUTYL-1-METHYL-7-(2-METHYLPHENYL)-1H-IMIDAZO[2,1-F]PURINE-2,4(3H,8H)-DIONE'>L87</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gk2\|4gk2]], [[4gk4\|4gk4]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">EphA3 ([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/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=4gk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gk3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gk3 RCSB], [http://www.ebi.ac.uk/pdbsum/4gk3 PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Inhibition of the tyrosine kinase erythropoietin-producing human hepatocellular carcinoma receptor B4 (EphB4) is an effective strategy for the treatment of solid tumors. We have previously reported a low nanomolar ATP-competitive inhibitor of EphB4 discovered in silico by fragment-based high-throughput docking combined with explicit solvent molecular dynamics simulations. Here we present a second generation of EphB4 inhibitors that show high inhibitory potency in both enzymatic and cell-based assays while preserving the appealing selectivity profile exhibited by the parent compound. In addition, respectable levels of antiproliferative activity for these compounds have been obtained. Finally, the binding mode predicted by docking and molecular dynamics simulations is validated by solving the crystal structures of three members of this chemical class in complex with the EphA3 tyrosine kinase whose ATP-binding site is essentially identical to that of EphB4.

-	~~{{STRUCTURE_4gk3\| PDB=4gk3 \| SCENE= }}~~	+	Optimization of Inhibitors of the Tyrosine Kinase EphB4. 2. Cellular Potency Improvement and Binding Mode Validation by X-ray Crystallography.,Lafleur K, Dong J, Huang D, Caflisch A, Nevado C J Med Chem. 2013 Jan 10;56(1):84-96. doi: 10.1021/jm301187e. Epub 2012 Dec 19. PMID:23253074<ref>PMID:23253074</ref>

-	~~===Human EphA3 Kinase domain in complex with ligand 87===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_23253074}}~~	+	== References ==
-		+	<references/>
-	==~~About this Structure~~==	+	__TOC__
-	~~[[4gk3]] is a 1 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=4GK3 OCA].~~	+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: Caflisch, A.]]	+	[[Category: Caflisch, A]]
-	[[Category: Dong, J.]]	+	[[Category: Dong, J]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
	[[Category: Membrane]]		[[Category: Membrane]]

OCA at 11:41, 23 January 2013

2013-01-23T11:41:55Z

←Older revision		Revision as of 11:41, 23 January 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4gk3.jpg\|left\|200px]]

-	~~The entry~~ 4gk3 ~~is ON HOLD~~ ~~until Paper Publication~~	+	{{STRUCTURE_4gk3\| PDB=4gk3 \| SCENE= }}

-	~~Authors: Dong, J., Caflisch, A.~~	+	===Human EphA3 Kinase domain in complex with ligand 87===

-	~~Description~~: ~~Human EphA3 Kinase domain in~~ complex ~~with ligand 87~~	+	{{ABSTRACT_PUBMED_23253074}}
		+
		+	==About this Structure==
		+	[[4gk3]] is a 1 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=4GK3 OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Receptor protein-tyrosine kinase]]
		+	[[Category: Caflisch, A.]]
		+	[[Category: Dong, J.]]
		+	[[Category: Atp-binding]]
		+	[[Category: Membrane]]
		+	[[Category: Phosphorylation]]
		+	[[Category: Receptor tyrosine kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 08:34, 31 October 2012

2012-10-31T08:34:37Z

←Older revision		Revision as of 08:34, 31 October 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4gk3 is ON HOLD	+	The entry 4gk3 is ON HOLD until Paper Publication

	Authors: Dong, J., Caflisch, A.		Authors: Dong, J., Caflisch, A.

	Description: Human EphA3 Kinase domain in complex with ligand 87		Description: Human EphA3 Kinase domain in complex with ligand 87

OCA: Protected "4gk3" [edit=sysop:move=sysop]

2012-08-22T05:35:27Z

Protected "4gk3" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:35, 22 August 2012

OCA: New page: '''Unreleased structure''' The entry 4gk3 is ON HOLD Authors: Dong, J., Caflisch, A. Description: Human EphA3 Kinase domain in complex with ligand 87

2012-08-22T05:35:26Z

New page: '''Unreleased structure''' The entry 4gk3 is ON HOLD Authors: Dong, J., Caflisch, A. Description: Human EphA3 Kinase domain in complex with ligand 87

New page

'''Unreleased structure'''

The entry 4gk3 is ON HOLD

Authors: Dong, J., Caflisch, A.

Description: Human EphA3 Kinase domain in complex with ligand 87