1y6a - Revision history

OCA at 08:55, 14 February 2024

OCA — Wed, 14 Feb 2024 08:55:13 GMT

←Older revision		Revision as of 08:55, 14 February 2024
Line 3:		Line 3:
	<StructureSection load='1y6a' size='340' side='right'caption='[[1y6a]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='1y6a' size='340' side='right'caption='[[1y6a]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1y6a]] 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=1Y6A OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=1Y6A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1y6a]] 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=1Y6A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y6A FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=AAZ:N~~-~~[5-(ETHYLSULFONYL)-2-METHOXYPHENYL]-5-[3-(2-PYRIDINYL)PHENYL]-1~~,~~3-OXAZOL-2-AMINE'>AAZ</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]] 2.1Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>~~[[~~Related_structure~~\|~~Related:~~]]~~</b></td><td class="sblockDat"><div style='overflow: auto~~; ~~max-height: 3em;'>[[1vr2\|1vr2]], [[1y6b\|1y6b]]</div>~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AAZ:N-[5-(ETHYLSULFONYL)-2-METHOXYPHENYL]-5-[3-(2-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-AMINE'>AAZ</scene></td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>KDR, FLK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9606 HUMAN])</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=1y6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y6a OCA], [https://pdbe.org/1y6a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y6a RCSB], [https://www.ebi.ac.uk/pdbsum/1y6a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y6a ProSAT]</span></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks'>~~[~~http://en.wikipedia.org/wiki/Transferase Transferase~~]~~, with EC number~~ [~~http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=~~2~~.7.10.~~1 ~~and~~ 2~~.7.10.2 2.7.10.1 and 2.7.10.2]~~ </~~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=1y6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y6a OCA], [~~http~~://pdbe.org/1y6a PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1y6a RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1y6a PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1y6a ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/VGFR2_HUMAN VGFR2_HUMAN]] Defects in KDR are associated with susceptibility to hemangioma capillary infantile (HCI) [MIM:[~~http~~://omim.org/entry/602089 602089]]. HCI are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. They are the most common tumor of infancy, occurring in up to 10% of all births. Hemangiomas tend to appear shortly after birth and show rapid neonatal growth for up to 12 months characterized by endothelial hypercellularity and increased numbers of mast cells. This phase is followed by slow involution at a rate of about 10% per year and replacement by fibrofatty stroma.<ref>PMID:11807987</ref> <ref>PMID:18931684</ref> Note=Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.	+	[https://www.uniprot.org/uniprot/VGFR2_HUMAN VGFR2_HUMAN] Defects in KDR are associated with susceptibility to hemangioma capillary infantile (HCI) [MIM:[https://omim.org/entry/602089 602089]. HCI are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. They are the most common tumor of infancy, occurring in up to 10% of all births. Hemangiomas tend to appear shortly after birth and show rapid neonatal growth for up to 12 months characterized by endothelial hypercellularity and increased numbers of mast cells. This phase is followed by slow involution at a rate of about 10% per year and replacement by fibrofatty stroma.<ref>PMID:11807987</ref> <ref>PMID:18931684</ref> Note=Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/VGFR2_HUMAN VGFR2_HUMAN]] Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC.<ref>PMID:19668192</ref> <ref>PMID:1417831</ref> <ref>PMID:7929439</ref> <ref>PMID:9160888</ref> <ref>PMID:9837777</ref> <ref>PMID:9804796</ref> <ref>PMID:10600473</ref> <ref>PMID:10102632</ref> <ref>PMID:11387210</ref> <ref>PMID:12649282</ref> <ref>PMID:15026417</ref> <ref>PMID:15215251</ref> <ref>PMID:15962004</ref> <ref>PMID:16966330</ref> <ref>PMID:17303569</ref> <ref>PMID:19834490</ref> <ref>PMID:20179233</ref> <ref>PMID:20224550</ref> <ref>PMID:20705758</ref> <ref>PMID:10368301</ref> <ref>PMID:18529047</ref> <ref>PMID:20080685</ref>	+	[https://www.uniprot.org/uniprot/VGFR2_HUMAN VGFR2_HUMAN] Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC.<ref>PMID:19668192</ref> <ref>PMID:1417831</ref> <ref>PMID:7929439</ref> <ref>PMID:9160888</ref> <ref>PMID:9837777</ref> <ref>PMID:9804796</ref> <ref>PMID:10600473</ref> <ref>PMID:10102632</ref> <ref>PMID:11387210</ref> <ref>PMID:12649282</ref> <ref>PMID:15026417</ref> <ref>PMID:15215251</ref> <ref>PMID:15962004</ref> <ref>PMID:16966330</ref> <ref>PMID:17303569</ref> <ref>PMID:19834490</ref> <ref>PMID:20179233</ref> <ref>PMID:20224550</ref> <ref>PMID:20705758</ref> <ref>PMID:10368301</ref> <ref>PMID:18529047</ref> <ref>PMID:20080685</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 24:		Line 22:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1y6a ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1y6a ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	A series of derivatives of 2-anilino-5-phenyloxazole (5) has been identified as inhibitors of VEGFR2 kinase. Herein we describe the structure-activity relationship (SAR) of this novel template. Optimization of both aryl rings led to very potent inhibitors at both the enzymatic and cellular levels. Oxazole 39 had excellent solubility and good oral PK when dosed as the bis-mesylate salt and demonstrated moderate in vivo efficacy against HT29 human colon tumor xenografts. X-ray crystallography confirmed the proposed binding mode, and comparison of oxazoles 39 and 46 revealed interesting differences in orientation of 2-pyridyl and 3-pyridyl rings, respectively, attached at the meta position of the 5-phenyl ring.
-
-	Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors.,Harris PA, Cheung M, Hunter RN 3rd, Brown ML, Veal JM, Nolte RT, Wang L, Liu W, Crosby RM, Johnson JH, Epperly AH, Kumar R, Luttrell DK, Stafford JA J Med Chem. 2005 Mar 10;48(5):1610-9. PMID:15743202<ref>PMID:15743202</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1y6a" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
-	*[[~~Vascular Endothelial Growth Factor Receptor~~\|~~Vascular Endothelial Growth Factor Receptor~~]]	+	*[[3D structures of vascular endothelial growth factor receptor\|3D structures of vascular endothelial growth factor receptor]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Transferase]]~~	+	[[Category: Brown ML]]
-	[[Category: Brown~~, M L~~]]	+	[[Category: Cheung M]]
-	[[Category: Cheung, M]]	+	[[Category: Crosby RM]]
-	[[Category: Crosby~~, R M~~]]	+	[[Category: Epperly AH]]
-	[[Category: Epperly~~, A H~~]]	+	[[Category: Harris PA]]
-	[[Category: Harris~~, P A~~]]	+	[[Category: Hunter RN]]
-	[[Category: Hunter~~, R N~~]]	+	[[Category: Johnson JH]]
-	[[Category: Johnson~~, J H~~]]	+	[[Category: Kumar R]]
-	[[Category: Kumar, R]]	+	[[Category: Liu W]]
-	[[Category: Liu, W]]	+	[[Category: Luttrell DK]]
-	[[Category: Luttrell~~, D K~~]]	+	[[Category: Nolte RT]]
-	[[Category: Nolte~~, R T~~]]	+	[[Category: Stafford JA]]
-	[[Category: Stafford~~, J A~~]]	+	[[Category: Veal JM]]
-	[[Category: Veal~~, J M~~]]	+	[[Category: Wang L]]
-	[[Category: Wang, L]]	+

OCA at 10:36, 6 January 2021

OCA — Wed, 06 Jan 2021 10:36:16 GMT

←Older revision		Revision as of 10:36, 6 January 2021
Line 1:		Line 1:

	==Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor==		==Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor==
-	<StructureSection load='1y6a' size='340' side='right' caption='[[1y6a]], [[Resolution\|resolution]] 2.10Å' scene=''>	+	<StructureSection load='1y6a' size='340' side='right'caption='[[1y6a]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1y6a]] 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=1Y6A OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1Y6A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1y6a]] 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=1Y6A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1Y6A FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AAZ:N-[5-(ETHYLSULFONYL)-2-METHOXYPHENYL]-5-[3-(2-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-AMINE'>AAZ</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AAZ:N-[5-(ETHYLSULFONYL)-2-METHOXYPHENYL]-5-[3-(2-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-AMINE'>AAZ</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1vr2\|1vr2]], [[1y6b\|1y6b]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1vr2\|1vr2]], [[1y6b\|1y6b]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KDR, FLK1 ([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">KDR, FLK1 ([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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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=1y6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y6a OCA], [http://pdbe.org/1y6a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1y6a RCSB], [http://www.ebi.ac.uk/pdbsum/1y6a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1y6a 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=1y6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y6a OCA], [http://pdbe.org/1y6a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1y6a RCSB], [http://www.ebi.ac.uk/pdbsum/1y6a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1y6a ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 18:		Line 18:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/y6/1y6a_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/y6/1y6a_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 33:		Line 33:
	</div>		</div>
	<div class="pdbe-citations 1y6a" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1y6a" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Vascular Endothelial Growth Factor Receptor\|Vascular Endothelial Growth Factor Receptor]]
	== References ==		== References ==
	<references/>		<references/>
Line 38:		Line 41:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Brown, M L]]		[[Category: Brown, M L]]

OCA at 10:06, 12 October 2017

OCA — Thu, 12 Oct 2017 10:06:51 GMT

←Older revision		Revision as of 10:06, 12 October 2017
Line 1:		Line 1:
		+
	==Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor==		==Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor==
	<StructureSection load='1y6a' size='340' side='right' caption='[[1y6a]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='1y6a' size='340' side='right' caption='[[1y6a]], [[Resolution\|resolution]] 2.10Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KDR, FLK1 ([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">KDR, FLK1 ([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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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=1y6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y6a OCA], [http://pdbe.org/1y6a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1y6a RCSB], [http://www.ebi.ac.uk/pdbsum/1y6a 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=1y6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y6a OCA], [http://pdbe.org/1y6a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1y6a RCSB], [http://www.ebi.ac.uk/pdbsum/1y6a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1y6a ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1y6a ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 32:		Line 33:
	</div>		</div>
	<div class="pdbe-citations 1y6a" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1y6a" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Vascular Endothelial Growth Factor Receptor\|Vascular Endothelial Growth Factor Receptor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:16, 11 September 2015

OCA — Fri, 11 Sep 2015 17:16:02 GMT

←Older revision		Revision as of 17:16, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='1y6a' size='340' side='right' caption='[[1y6a]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='1y6a' size='340' side='right' caption='[[1y6a]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1y6a]] 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=1Y6A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Y6A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1y6a]] 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=1Y6A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Y6A FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AAZ:N-[5-(ETHYLSULFONYL)-2-METHOXYPHENYL]-5-[3-(2-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-AMINE'>AAZ</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AAZ:N-[5-(ETHYLSULFONYL)-2-METHOXYPHENYL]-5-[3-(2-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-AMINE'>AAZ</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1vr2\|1vr2]], [[1y6b\|1y6b]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1vr2\|1vr2]], [[1y6b\|1y6b]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KDR, FLK1 ([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">KDR, FLK1 ([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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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=1y6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y6a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1y6a RCSB], [http://www.ebi.ac.uk/pdbsum/1y6a 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=1y6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y6a OCA], [http://pdbe.org/1y6a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1y6a RCSB], [http://www.ebi.ac.uk/pdbsum/1y6a PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 31:		Line 31:
	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 1y6a" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Brown, M L]]		[[Category: Brown, M L]]

OCA at 09:53, 8 January 2015

OCA — Thu, 08 Jan 2015 09:53:18 GMT

←Older revision		Revision as of 09:53, 8 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1y6a]] 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=1Y6A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Y6A FirstGlance]. <br>		<table><tr><td colspan='2'>[[1y6a]] 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=1Y6A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Y6A FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AAZ:N-[5-(ETHYLSULFONYL)-2-METHOXYPHENYL]-5-[3-(2-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-AMINE'>AAZ</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AAZ:N-[5-(ETHYLSULFONYL)-2-METHOXYPHENYL]-5-[3-(2-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-AMINE'>AAZ</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1vr2\|1vr2]], [[1y6b\|1y6b]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1vr2\|1vr2]], [[1y6b\|1y6b]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KDR, FLK1 ([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">KDR, FLK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1y6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y6a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1y6a RCSB], [http://www.ebi.ac.uk/pdbsum/1y6a 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=1y6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y6a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1y6a RCSB], [http://www.ebi.ac.uk/pdbsum/1y6a PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/VGFR2_HUMAN VGFR2_HUMAN]] Defects in KDR are associated with susceptibility to hemangioma capillary infantile (HCI) [MIM:[http://omim.org/entry/602089 602089]]. HCI are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. They are the most common tumor of infancy, occurring in up to 10% of all births. Hemangiomas tend to appear shortly after birth and show rapid neonatal growth for up to 12 months characterized by endothelial hypercellularity and increased numbers of mast cells. This phase is followed by slow involution at a rate of about 10% per year and replacement by fibrofatty stroma.<ref>PMID:11807987</ref> <ref>PMID:18931684</ref> Note=Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.		[[http://www.uniprot.org/uniprot/VGFR2_HUMAN VGFR2_HUMAN]] Defects in KDR are associated with susceptibility to hemangioma capillary infantile (HCI) [MIM:[http://omim.org/entry/602089 602089]]. HCI are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. They are the most common tumor of infancy, occurring in up to 10% of all births. Hemangiomas tend to appear shortly after birth and show rapid neonatal growth for up to 12 months characterized by endothelial hypercellularity and increased numbers of mast cells. This phase is followed by slow involution at a rate of about 10% per year and replacement by fibrofatty stroma.<ref>PMID:11807987</ref> <ref>PMID:18931684</ref> Note=Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
Line 40:		Line 40:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Transferase]]		[[Category: Transferase]]
-	[[Category: Brown, M L.]]	+	[[Category: Brown, M L]]
-	[[Category: Cheung, M.]]	+	[[Category: Cheung, M]]
-	[[Category: Crosby, R M.]]	+	[[Category: Crosby, R M]]
-	[[Category: Epperly, A H.]]	+	[[Category: Epperly, A H]]
-	[[Category: Harris, P A.]]	+	[[Category: Harris, P A]]
-	[[Category: Hunter, R N.]]	+	[[Category: Hunter, R N]]
-	[[Category: Johnson, J H.]]	+	[[Category: Johnson, J H]]
-	[[Category: Kumar, R.]]	+	[[Category: Kumar, R]]
-	[[Category: Liu, W.]]	+	[[Category: Liu, W]]
-	[[Category: Luttrell, D K.]]	+	[[Category: Luttrell, D K]]
-	[[Category: Nolte, R T.]]	+	[[Category: Nolte, R T]]
-	[[Category: Stafford, J A.]]	+	[[Category: Stafford, J A]]
-	[[Category: Veal, J M.]]	+	[[Category: Veal, J M]]
-	[[Category: Wang, L~~.]]~~	+	[[Category: Wang, L]]
-	~~[[Category: Transferase~~]]	+

OCA at 18:49, 29 September 2014

OCA — Mon, 29 Sep 2014 18:49:48 GMT

←Older revision		Revision as of 18:49, 29 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1y6a\| PDB=1y6a \| SCENE= }}~~	+	==Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor==
-	===Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor===	+	<StructureSection load='1y6a' size='340' side='right' caption='[[1y6a]], [[Resolution\|resolution]] 2.10Å' scene=''>
-	~~{{ABSTRACT_PUBMED_15743202}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1y6a]] 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=1Y6A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Y6A FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AAZ:N-[5-(ETHYLSULFONYL)-2-METHOXYPHENYL]-5-[3-(2-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-AMINE'>AAZ</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1vr2\|1vr2]], [[1y6b\|1y6b]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KDR, FLK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1y6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y6a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1y6a RCSB], [http://www.ebi.ac.uk/pdbsum/1y6a PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/VGFR2_HUMAN VGFR2_HUMAN]] Defects in KDR are associated with susceptibility to hemangioma capillary infantile (HCI) [MIM:[http://omim.org/entry/602089 602089]]. HCI are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. They are the most common tumor of infancy, occurring in up to 10% of all births. Hemangiomas tend to appear shortly after birth and show rapid neonatal growth for up to 12 months characterized by endothelial hypercellularity and increased numbers of mast cells. This phase is followed by slow involution at a rate of about 10% per year and replacement by fibrofatty stroma.<ref>PMID:11807987</ref> <ref>PMID:18931684</ref> Note=Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/VGFR2_HUMAN VGFR2_HUMAN]] Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC.<ref>PMID:19668192</ref> <ref>PMID:1417831</ref> <ref>PMID:7929439</ref> <ref>PMID:9160888</ref> <ref>PMID:9837777</ref> <ref>PMID:9804796</ref> <ref>PMID:10600473</ref> <ref>PMID:10102632</ref> <ref>PMID:11387210</ref> <ref>PMID:12649282</ref> <ref>PMID:15026417</ref> <ref>PMID:15215251</ref> <ref>PMID:15962004</ref> <ref>PMID:16966330</ref> <ref>PMID:17303569</ref> <ref>PMID:19834490</ref> <ref>PMID:20179233</ref> <ref>PMID:20224550</ref> <ref>PMID:20705758</ref> <ref>PMID:10368301</ref> <ref>PMID:18529047</ref> <ref>PMID:20080685</ref>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/y6/1y6a_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A series of derivatives of 2-anilino-5-phenyloxazole (5) has been identified as inhibitors of VEGFR2 kinase. Herein we describe the structure-activity relationship (SAR) of this novel template. Optimization of both aryl rings led to very potent inhibitors at both the enzymatic and cellular levels. Oxazole 39 had excellent solubility and good oral PK when dosed as the bis-mesylate salt and demonstrated moderate in vivo efficacy against HT29 human colon tumor xenografts. X-ray crystallography confirmed the proposed binding mode, and comparison of oxazoles 39 and 46 revealed interesting differences in orientation of 2-pyridyl and 3-pyridyl rings, respectively, attached at the meta position of the 5-phenyl ring.

-	~~==Disease==~~	+	Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors.,Harris PA, Cheung M, Hunter RN 3rd, Brown ML, Veal JM, Nolte RT, Wang L, Liu W, Crosby RM, Johnson JH, Epperly AH, Kumar R, Luttrell DK, Stafford JA J Med Chem. 2005 Mar 10;48(5):1610-9. PMID:15743202<ref>PMID:15743202</ref>
-	~~[[http://www~~.~~uniprot~~.~~org/uniprot/VGFR2_HUMAN VGFR2_HUMAN]] Defects in KDR are associated with susceptibility to hemangioma capillary infantile~~ (~~HCI~~) ~~[MIM~~:~~[http://omim~~.org/entry/602089 602089]]. HCI are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. They are the most common tumor of infancy, occurring in up to 10% of all births. Hemangiomas tend to appear shortly after birth and show rapid neonatal growth for up to 12 months characterized by endothelial hypercellularity and increased numbers of mast cells. This phase is followed by slow involution at a rate of about 10% per year and replacement by fibrofatty stroma.<ref>PMID:~~11807987</ref>~~<ref>PMID:~~18931684~~</ref> ~~Note=Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.~~	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~/~~/www.uniprot.org/uniprot/VGFR2_HUMAN VGFR2_HUMAN]] Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA~~, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a ~~transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator~~ of ~~VEGFA- and VEGFC-mediated lymphangiogenesis by limiting~~ the ~~amount of free VEGFA and/or VEGFC and preventing their binding to FLT4~~. ~~Modulates FLT1 and FLT4 signaling by forming heterodimers~~. ~~Binding~~ of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC.<~~ref~~>~~PMID:19668192~~</~~ref~~><ref>PMID:1417831</ref><ref>PMID:7929439</ref><ref>PMID:9160888</ref><ref>PMID:9837777</ref><ref>PMID:9804796</ref><ref>PMID:10600473</ref><ref>PMID:10102632</ref><ref>PMID:11387210</ref><ref>PMID:12649282</ref><ref>PMID:15026417</ref><ref>PMID:15215251</ref><ref>PMID:15962004</ref><ref>PMID:16966330</ref><ref>PMID:17303569</ref><ref>PMID:19834490</ref><ref>PMID:20179233</ref><ref>PMID:20224550</ref><ref>PMID:20705758</ref><ref>PMID:10368301</ref><ref>PMID:18529047</ref><ref>PMID:20080685</ref>	+	</div>
-		+
-	~~==About this Structure==~~	+
-	[[1y6a]] 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=1Y6A OCA].	+

	==See Also==		==See Also==
	*[[Vascular Endothelial Growth Factor Receptor\|Vascular Endothelial Growth Factor Receptor]]		*[[Vascular Endothelial Growth Factor Receptor\|Vascular Endothelial Growth Factor Receptor]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:015743202</ref><ref group="xtra">PMID:018529047</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 23:44, 24 March 2013

OCA — Sun, 24 Mar 2013 23:44:05 GMT

←Older revision		Revision as of 23:44, 24 March 2013
Line 1:		Line 1:
-	[[Image:1y6a.png\|left\|200px]]
-
	{{STRUCTURE_1y6a\| PDB=1y6a \| SCENE= }}		{{STRUCTURE_1y6a\| PDB=1y6a \| SCENE= }}
-
	===Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor===		===Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor===
		+	{{ABSTRACT_PUBMED_15743202}}

-	~~{{ABSTRACT_PUBMED_15743202}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/VGFR2_HUMAN VGFR2_HUMAN]] Defects in KDR are associated with susceptibility to hemangioma capillary infantile (HCI) [MIM:[http://omim.org/entry/602089 602089]]. HCI are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. They are the most common tumor of infancy, occurring in up to 10% of all births. Hemangiomas tend to appear shortly after birth and show rapid neonatal growth for up to 12 months characterized by endothelial hypercellularity and increased numbers of mast cells. This phase is followed by slow involution at a rate of about 10% per year and replacement by fibrofatty stroma.<ref>PMID:11807987</ref><ref>PMID:18931684</ref> Note=Plays a major role in tumor angiogenesis. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions.
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/VGFR2_HUMAN VGFR2_HUMAN]] Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and embryonic hematopoiesis. Promotes proliferation, survival, migration and differentiation of endothelial cells. Promotes reorganization of the actin cytoskeleton. Isoforms lacking a transmembrane domain, such as isoform 2 and isoform 3, may function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Isoform 2 plays an important role as negative regulator of VEGFA- and VEGFC-mediated lymphangiogenesis by limiting the amount of free VEGFA and/or VEGFC and preventing their binding to FLT4. Modulates FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular growth factors to isoform 1 leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton and activation of PTK2/FAK1. Required for VEGFA-mediated induction of NOS2 and NOS3, leading to the production of the signaling molecule nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC.<ref>PMID:19668192</ref><ref>PMID:1417831</ref><ref>PMID:7929439</ref><ref>PMID:9160888</ref><ref>PMID:9837777</ref><ref>PMID:9804796</ref><ref>PMID:10600473</ref><ref>PMID:10102632</ref><ref>PMID:11387210</ref><ref>PMID:12649282</ref><ref>PMID:15026417</ref><ref>PMID:15215251</ref><ref>PMID:15962004</ref><ref>PMID:16966330</ref><ref>PMID:17303569</ref><ref>PMID:19834490</ref><ref>PMID:20179233</ref><ref>PMID:20224550</ref><ref>PMID:20705758</ref><ref>PMID:10368301</ref><ref>PMID:18529047</ref><ref>PMID:20080685</ref>

	==About this Structure==		==About this Structure==
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	==Reference==		==Reference==
-	<ref group="xtra">PMID:015743202</ref><ref group="xtra">PMID:018529047</ref><references group="xtra"/>	+	<ref group="xtra">PMID:015743202</ref><ref group="xtra">PMID:018529047</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 20:33, 20 October 2012

OCA — Sat, 20 Oct 2012 20:33:26 GMT

←Older revision		Revision as of 20:33, 20 October 2012
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	==About this Structure==		==About this Structure==
-	[[1y6a]] is a 1 chain structure ~~of [[Vascular Endothelial Growth Factor Receptor]]~~ 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=1Y6A OCA].	+	[[1y6a]] 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=1Y6A OCA].

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

OCA at 10:53, 27 July 2012

OCA — Fri, 27 Jul 2012 10:53:21 GMT

←Older revision		Revision as of 10:53, 27 July 2012
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	[[Image:1y6a.png\|left\|200px]]		[[Image:1y6a.png\|left\|200px]]

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	{{STRUCTURE_1y6a\| PDB=1y6a \| SCENE= }}		{{STRUCTURE_1y6a\| PDB=1y6a \| SCENE= }}

	===Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor===		===Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor===

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	{{ABSTRACT_PUBMED_15743202}}		{{ABSTRACT_PUBMED_15743202}}

OCA: Protected "1y6a" [edit=sysop:move=sysop]

OCA — Sat, 02 Jun 2012 15:17:01 GMT

Protected "1y6a" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:17, 2 June 2012