3wze - Revision history

OCA at 05:36, 10 August 2022

OCA — Wed, 10 Aug 2022 05:36:24 GMT

←Older revision		Revision as of 05:36, 10 August 2022
Line 1:		Line 1:

	==KDR in complex with ligand sorafenib==		==KDR in complex with ligand sorafenib==
-	<StructureSection load='3wze' size='340' side='right' caption='[[3wze]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='3wze' size='340' side='right'caption='[[3wze]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3wze]] 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=3WZE OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3WZE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3wze]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WZE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WZE FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BAX:4-{4-[({[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-N-METHYLPYRIDINE-2-CARBOXAMIDE'>BAX</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BAX:4-{4-[({[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-N-METHYLPYRIDINE-2-CARBOXAMIDE'>BAX</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3wzd\|3wzd]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3wzd\|3wzd]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KDR, FLK1, VEGFR2 ([~~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, VEGFR2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/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'>[https://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [https://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=3wze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wze OCA], [~~http~~://pdbe.org/3wze PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3wze RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3wze PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3wze 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=3wze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wze OCA], [https://pdbe.org/3wze PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wze RCSB], [https://www.ebi.ac.uk/pdbsum/3wze PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wze 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 25:

	==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/>
Line 31:		Line 31:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Ikemori_Kawada, M]]		[[Category: Ikemori_Kawada, M]]

OCA at 09:20, 21 February 2019

OCA — Thu, 21 Feb 2019 09:20:58 GMT

←Older revision		Revision as of 09:20, 21 February 2019
Line 3:		Line 3:
	<StructureSection load='3wze' size='340' side='right' caption='[[3wze]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='3wze' size='340' side='right' caption='[[3wze]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3wze]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WZE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WZE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3wze]] 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=3WZE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WZE FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BAX:4-{4-[({[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-N-METHYLPYRIDINE-2-CARBOXAMIDE'>BAX</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BAX:4-{4-[({[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-N-METHYLPYRIDINE-2-CARBOXAMIDE'>BAX</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3wzd\|3wzd]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3wzd\|3wzd]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KDR, FLK1, VEGFR2 ([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=3wze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wze OCA], [http://pdbe.org/3wze PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wze RCSB], [http://www.ebi.ac.uk/pdbsum/3wze PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wze 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=3wze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wze OCA], [http://pdbe.org/3wze PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wze RCSB], [http://www.ebi.ac.uk/pdbsum/3wze PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wze ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Ikemori_Kawada, M]]		[[Category: Ikemori_Kawada, M]]

OCA at 17:37, 9 March 2017

OCA — Thu, 09 Mar 2017 17:37:41 GMT

←Older revision		Revision as of 17:37, 9 March 2017
Line 1:		Line 1:
		+
	==KDR in complex with ligand sorafenib==		==KDR in complex with ligand sorafenib==
	<StructureSection load='3wze' size='340' side='right' caption='[[3wze]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='3wze' size='340' side='right' caption='[[3wze]], [[Resolution\|resolution]] 1.90Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3wzd\|3wzd]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3wzd\|3wzd]]</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=3wze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wze OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wze RCSB], [http://www.ebi.ac.uk/pdbsum/3wze 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=3wze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wze OCA], [http://pdbe.org/3wze PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wze RCSB], [http://www.ebi.ac.uk/pdbsum/3wze PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wze ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	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 3wze" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Vascular Endothelial Growth Factor Receptor\|Vascular Endothelial Growth Factor Receptor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 15:54, 27 May 2015

OCA — Wed, 27 May 2015 15:54:04 GMT

←Older revision		Revision as of 15:54, 27 May 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==KDR in complex with ligand sorafenib==
		+	<StructureSection load='3wze' size='340' side='right' caption='[[3wze]], [[Resolution\|resolution]] 1.90Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3wze]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WZE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WZE FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BAX:4-{4-[({[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-N-METHYLPYRIDINE-2-CARBOXAMIDE'>BAX</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3wzd\|3wzd]]</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=3wze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wze OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3wze RCSB], [http://www.ebi.ac.uk/pdbsum/3wze 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Lenvatinib is an oral multikinase inhibitor that selectively inhibits vascular endothelial growth factor (VEGF) receptors 1 to 3 and other proangiogenic and oncogenic pathway-related receptor tyrosine kinases. To elucidate the origin of the potency of lenvatinib in VEGF receptor 2 (VEGFR2) inhibition, we conducted a kinetic interaction analysis of lenvatinib with VEGFR2 and X-ray analysis of the crystal structure of VEGFR2-lenvatinib complexes. Kinetic analysis revealed that lenvatinib had a rapid association rate constant and a relatively slow dissociation rate constant in complex with VEGFR2. Co-crystal structure analysis demonstrated that lenvatinib binds at its ATP mimetic quinoline moiety to the ATP binding site and to the neighboring region via a cyclopropane ring, adopting an Asp-Phe-Gly (DFG)-"in" conformation. These results suggest that lenvatinib is very distinct in its binding mode of interaction compared to the several approved VEGFR2 kinase inhibitors.

-	~~The entry 3wze is ON HOLD~~	+	Distinct binding mode of multikinase inhibitor lenvatinib revealed by biochemical characterization.,Okamoto K, Ikemori-Kawada M, Jestel A, von Konig K, Funahashi Y, Matsushima T, Tsuruoka A, Inoue A, Matsui J ACS Med Chem Lett. 2014 Nov 17;6(1):89-94. doi: 10.1021/ml500394m. eCollection, 2015 Jan 8. PMID:25589937<ref>PMID:25589937</ref>

-	~~Authors: Okamoto~~, K.~~, Ikemori_Kawada, M~~.~~, Inoue, A., Matsui, J~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~KDR in complex with ligand sorafenib~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Receptor protein-tyrosine kinase]]
		+	[[Category: Ikemori_Kawada, M]]
	[[Category: Inoue, A]]		[[Category: Inoue, A]]
-	[[Category: ~~Ikemori_kawada~~, M]]	+	[[Category: Matsui, J]]
	[[Category: Okamoto, K]]		[[Category: Okamoto, K]]
-	[[Category: ~~Matsui, J~~]]	+	[[Category: Kdr receptor kinase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 06:14, 30 April 2015

OCA — Thu, 30 Apr 2015 06:14:44 GMT

←Older revision		Revision as of 06:14, 30 April 2015
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	Authors: Okamoto, K., Ikemori_Kawada, M., Inoue, A., Matsui, J.		Authors: Okamoto, K., Ikemori_Kawada, M., Inoue, A., Matsui, J.

-	Description: KDR ~~IN COMPLEX WITH LIGAND SORAFENIB~~	+	Description: KDR in complex with ligand sorafenib
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Inoue, A]]		[[Category: Inoue, A]]

OCA at 13:08, 24 December 2014

OCA — Wed, 24 Dec 2014 13:08:55 GMT

←Older revision		Revision as of 13:08, 24 December 2014
Line 6:		Line 6:

	Description: KDR IN COMPLEX WITH LIGAND SORAFENIB		Description: KDR IN COMPLEX WITH LIGAND SORAFENIB
		+	[[Category: Unreleased Structures]]
		+	[[Category: Inoue, A]]
		+	[[Category: Ikemori_kawada, M]]
		+	[[Category: Okamoto, K]]
		+	[[Category: Matsui, J]]

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

OCA — Wed, 01 Oct 2014 22:44:51 GMT

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

←Older revision

Revision as of 22:44, 1 October 2014

OCA: New page: '''Unreleased structure''' The entry 3wze is ON HOLD Authors: Okamoto, K., Ikemori_Kawada, M., Inoue, A., Matsui, J. Description: KDR IN COMPLEX WITH LIGAND SORAFENIB

OCA — Wed, 01 Oct 2014 22:44:50 GMT

New page: '''Unreleased structure''' The entry 3wze is ON HOLD Authors: Okamoto, K., Ikemori_Kawada, M., Inoue, A., Matsui, J. Description: KDR IN COMPLEX WITH LIGAND SORAFENIB

New page

'''Unreleased structure'''

The entry 3wze is ON HOLD

Authors: Okamoto, K., Ikemori_Kawada, M., Inoue, A., Matsui, J.

Description: KDR IN COMPLEX WITH LIGAND SORAFENIB