3f66 - Revision history

OCA at 00:28, 28 December 2023

2023-12-28T00:28:52Z

←Older revision		Revision as of 00:28, 28 December 2023
Line 3:		Line 3:
	<StructureSection load='3f66' size='340' side='right'caption='[[3f66]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='3f66' size='340' side='right'caption='[[3f66]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3f66]] is a 2 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=3F66 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F66 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3f66]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F66 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F66 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GBL:GAMMA-BUTYROLACTONE'>GBL</scene>, <scene name='pdbligand=IHX:3-[3-(4-METHYLPIPERAZIN-1-YL)-7-(TRIFLUOROMETHYL)QUINOXALIN-5-YL]PHENOL'>IHX</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.4Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MET ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GBL:GAMMA-BUTYROLACTONE'>GBL</scene>, <scene name='pdbligand=IHX:3-[3-(4-METHYLPIPERAZIN-1-YL)-7-(TRIFLUOROMETHYL)QUINOXALIN-5-YL]PHENOL'>IHX</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=3f66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f66 OCA], [https://pdbe.org/3f66 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f66 RCSB], [https://www.ebi.ac.uk/pdbsum/3f66 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f66 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=3f66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f66 OCA], [https://pdbe.org/3f66 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f66 RCSB], [https://www.ebi.ac.uk/pdbsum/3f66 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f66 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Note=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein. Note=Defects in MET may be associated with gastric cancer. Defects in MET are a cause of hepatocellular carcinoma (HCC) [MIM:[https://omim.org/entry/114550 114550]].<ref>PMID:9927037</ref> Defects in MET are a cause of renal cell carcinoma papillary (RCCP) [MIM:[https://omim.org/entry/605074 605074]]. It is a subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into common renal cell carcinoma (clear cell, non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:9140397</ref> <ref>PMID:9563489</ref> <ref>PMID:10433944</ref> <ref>PMID:10417759</ref> <ref>PMID:10327054</ref> Note=A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes. Note=MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies.<ref>PMID:20949619</ref>	+	[https://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN] Note=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein. Note=Defects in MET may be associated with gastric cancer. Defects in MET are a cause of hepatocellular carcinoma (HCC) [MIM:[https://omim.org/entry/114550 114550].<ref>PMID:9927037</ref> Defects in MET are a cause of renal cell carcinoma papillary (RCCP) [MIM:[https://omim.org/entry/605074 605074]. It is a subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into common renal cell carcinoma (clear cell, non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:9140397</ref> <ref>PMID:9563489</ref> <ref>PMID:10433944</ref> <ref>PMID:10417759</ref> <ref>PMID:10327054</ref> Note=A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes. Note=MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies.<ref>PMID:20949619</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref> Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref>	+	[https://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref> Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 39:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein-tyrosine kinase]]~~	+	[[Category: Ceska T]]
-	[[Category: Ceska, T]]	+	[[Category: Meier C]]
-	[[Category: Meier, C]]	+
-	~~[[Category: Alternative splicing]]~~	+
-	~~[[Category: Atp-binding]]~~	+
-	~~[[Category: C-met]]~~	+
-	~~[[Category: Chromosomal rearrangement]]~~	+
-	~~[[Category: Disease mutation]]~~	+
-	~~[[Category: Glycoprotein]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Nucleotide-binding]]~~	+
-	~~[[Category: Phosphoprotein]]~~	+
-	~~[[Category: Polymorphism]]~~	+
-	~~[[Category: Protein kinase]]~~	+
-	~~[[Category: Proto-oncogene]]~~	+
-	~~[[Category: Quinoxaline]]~~	+
-	~~[[Category: Receptor]]~~	+
-	~~[[Category: Repeat]]~~	+
-	~~[[Category: Signal]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transmembrane]]~~	+
-	~~[[Category: Tyrosine-protein kinase~~]]	+

OCA at 09:24, 23 February 2022

2022-02-23T09:24:36Z

←Older revision		Revision as of 09:24, 23 February 2022
Line 1:		Line 1:

	==Human c-Met Kinase in complex with quinoxaline inhibitor==		==Human c-Met Kinase in complex with quinoxaline inhibitor==
-	<StructureSection load='3f66' size='340' side='right' caption='[[3f66]], [[Resolution\|resolution]] 1.40Å' scene=''>	+	<StructureSection load='3f66' size='340' side='right'caption='[[3f66]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3f66]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F66 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3F66 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3f66]] is a 2 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=3F66 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F66 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GBL:GAMMA-BUTYROLACTONE'>GBL</scene>, <scene name='pdbligand=IHX:3-[3-(4-METHYLPIPERAZIN-1-YL)-7-(TRIFLUOROMETHYL)QUINOXALIN-5-YL]PHENOL'>IHX</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GBL:GAMMA-BUTYROLACTONE'>GBL</scene>, <scene name='pdbligand=IHX:3-[3-(4-METHYLPIPERAZIN-1-YL)-7-(TRIFLUOROMETHYL)QUINOXALIN-5-YL]PHENOL'>IHX</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MET ([~~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">MET ([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=3f66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f66 OCA], [~~http~~://pdbe.org/3f66 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3f66 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3f66 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3f66 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=3f66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f66 OCA], [https://pdbe.org/3f66 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f66 RCSB], [https://www.ebi.ac.uk/pdbsum/3f66 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f66 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Note=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein. Note=Defects in MET may be associated with gastric cancer. Defects in MET are a cause of hepatocellular carcinoma (HCC) [MIM:[~~http~~://omim.org/entry/114550 114550]].<ref>PMID:9927037</ref> Defects in MET are a cause of renal cell carcinoma papillary (RCCP) [MIM:[~~http~~://omim.org/entry/605074 605074]]. It is a subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into common renal cell carcinoma (clear cell, non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:9140397</ref> <ref>PMID:9563489</ref> <ref>PMID:10433944</ref> <ref>PMID:10417759</ref> <ref>PMID:10327054</ref> Note=A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes. Note=MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies.<ref>PMID:20949619</ref>	+	[[https://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Note=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein. Note=Defects in MET may be associated with gastric cancer. Defects in MET are a cause of hepatocellular carcinoma (HCC) [MIM:[https://omim.org/entry/114550 114550]].<ref>PMID:9927037</ref> Defects in MET are a cause of renal cell carcinoma papillary (RCCP) [MIM:[https://omim.org/entry/605074 605074]]. It is a subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into common renal cell carcinoma (clear cell, non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:9140397</ref> <ref>PMID:9563489</ref> <ref>PMID:10433944</ref> <ref>PMID:10417759</ref> <ref>PMID:10327054</ref> Note=A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes. Note=MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies.<ref>PMID:20949619</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref> Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref>	+	[[https://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref> Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 34:		Line 34:

	==See Also==		==See Also==
-	*[[Hepatocyte growth factor receptor\|Hepatocyte growth factor receptor]]	+	*[[Hepatocyte growth factor receptor 3D structures\|Hepatocyte growth factor receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 40:		Line 40:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Ceska, T]]		[[Category: Ceska, T]]

OCA at 21:51, 2 December 2018

2018-12-02T21:51:33Z

←Older revision		Revision as of 21:51, 2 December 2018
Line 17:		Line 17:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f6/3f66_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f6/3f66_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>

OCA at 14:57, 5 August 2016

2016-08-05T14:57:06Z

←Older revision		Revision as of 14:57, 5 August 2016
Line 1:		Line 1:
		+
	==Human c-Met Kinase in complex with quinoxaline inhibitor==		==Human c-Met Kinase in complex with quinoxaline inhibitor==
	<StructureSection load='3f66' size='340' side='right' caption='[[3f66]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='3f66' size='340' side='right' caption='[[3f66]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3f66]] is a 2 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=3F66 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F66 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3f66]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F66 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F66 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GBL:GAMMA-BUTYROLACTONE'>GBL</scene>, <scene name='pdbligand=IHX:3-[3-(4-METHYLPIPERAZIN-1-YL)-7-(TRIFLUOROMETHYL)QUINOXALIN-5-YL]PHENOL'>IHX</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GBL:GAMMA-BUTYROLACTONE'>GBL</scene>, <scene name='pdbligand=IHX:3-[3-(4-METHYLPIPERAZIN-1-YL)-7-(TRIFLUOROMETHYL)QUINOXALIN-5-YL]PHENOL'>IHX</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MET ([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">MET ([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=3f66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f66 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3f66 RCSB], [http://www.ebi.ac.uk/pdbsum/3f66 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=3f66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f66 OCA], [http://pdbe.org/3f66 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f66 RCSB], [http://www.ebi.ac.uk/pdbsum/3f66 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3f66 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	<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=3f66 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 30:		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 3f66" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 37:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Ceska, T]]		[[Category: Ceska, T]]

OCA at 13:54, 18 December 2014

2014-12-18T13:54:36Z

←Older revision		Revision as of 13:54, 18 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3f66~~\| ~~PDB~~=3f66 \| ~~SCENE~~= }}	+	==Human c-Met Kinase in complex with quinoxaline inhibitor==
-	===~~Human c~~-~~Met Kinase in complex~~ with ~~quinoxaline inhibitor~~===	+	<StructureSection load='3f66' size='340' side='right' caption='[[3f66]], [[Resolution\|resolution]] 1.40Å' scene=''>
-	~~{{ABSTRACT_PUBMED_19059779}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3f66]] is a 2 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=3F66 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F66 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GBL:GAMMA-BUTYROLACTONE'>GBL</scene>, <scene name='pdbligand=IHX:3-[3-(4-METHYLPIPERAZIN-1-YL)-7-(TRIFLUOROMETHYL)QUINOXALIN-5-YL]PHENOL'>IHX</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MET ([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=3f66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f66 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3f66 RCSB], [http://www.ebi.ac.uk/pdbsum/3f66 PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Note=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein. Note=Defects in MET may be associated with gastric cancer. Defects in MET are a cause of hepatocellular carcinoma (HCC) [MIM:[http://omim.org/entry/114550 114550]].<ref>PMID:9927037</ref> Defects in MET are a cause of renal cell carcinoma papillary (RCCP) [MIM:[http://omim.org/entry/605074 605074]]. It is a subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into common renal cell carcinoma (clear cell, non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:9140397</ref> <ref>PMID:9563489</ref> <ref>PMID:10433944</ref> <ref>PMID:10417759</ref> <ref>PMID:10327054</ref> Note=A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes. Note=MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies.<ref>PMID:20949619</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</ref> Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.<ref>PMID:1846706</ref> <ref>PMID:8182137</ref> <ref>PMID:15314156</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/f6/3f66_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 quinoxaline inhibitors of c-Met kinase is described. The postulated binding mode was confirmed by an X-ray crystal structure and optimisation of the series was performed on the basis of this structure. Future directions for development of the series are discussed together with the identification of a novel quinoline scaffold.

-	~~==Disease==~~	+	Discovery of a novel series of quinoxalines as inhibitors of c-Met kinase.,Porter J, Lumb S, Lecomte F, Reuberson J, Foley A, Calmiano M, le Riche K, Edwards H, Delgado J, Franklin RJ, Gascon-Simorte JM, Maloney A, Meier C, Batchelor M Bioorg Med Chem Lett. 2009 Jan 15;19(2):397-400. Epub 2008 Nov 21. PMID:19059779<ref>PMID:19059779</ref>
-	~~[[http://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Note=Activation~~ of ~~MET after rearrangement with the TPR gene produces an oncogenic protein. Note=Defects in MET may be associated with gastric cancer. Defects in MET are~~ a ~~cause~~ of ~~hepatocellular carcinoma (HCC) [MIM:[http://omim.org/entry/114550 114550]].<ref>PMID:9927037</ref> Defects in MET are a cause~~ of ~~renal cell carcinoma papillary (RCCP) [MIM:[http://omim~~.~~org/entry/605074 605074]]. It is a subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous~~, ~~irregular~~, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into common renal cell carcinoma (clear cell, ~~non-papillary carcinoma)~~, ~~papillary renal cell carcinoma~~, ~~chromophobe renal cell carcinoma~~, ~~collecting duct carcinoma with medullary carcinoma of the kidney~~, ~~and unclassified renal cell carcinoma.<ref>PMID:9140397</ref><ref>PMID:9563489</ref><ref>PMID:10433944</ref><ref>PMID:10417759</ref><ref>PMID:10327054</ref> Note=~~A ~~common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families~~. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes. Note=MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (~~CUP~~) ~~or primary occult malignancy~~. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies.<ref>PMID:~~20949619~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~//www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, ~~scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation~~ of ~~MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or~~ the ~~adapter GAB1~~. ~~Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC~~. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells.<~~ref~~>~~PMID:1846706~~</~~ref~~><ref>PMID:8182137</ref><ref>PMID:15314156</ref> Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.<ref>PMID:1846706</ref><ref>PMID:8182137</ref><ref>PMID:15314156</ref>	+	</div>
-		+
-	~~==About this Structure==~~	+
-	[[3f66]] is a 2 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=3F66 OCA].	+

	==See Also==		==See Also==
	*[[Hepatocyte growth factor receptor\|Hepatocyte growth factor receptor]]		*[[Hepatocyte growth factor receptor\|Hepatocyte growth factor receptor]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:019059779</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: Ceska, T.]]	+	[[Category: Ceska, T]]
-	[[Category: Meier, C.]]	+	[[Category: Meier, C]]
	[[Category: Alternative splicing]]		[[Category: Alternative splicing]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
Line 40:		Line 60:
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Transmembrane]]		[[Category: Transmembrane]]
-	[[Category: Tyrosine-protein kinase.]]	+	[[Category: Tyrosine-protein kinase]]

OCA at 00:23, 25 March 2013

2013-03-25T00:23:47Z

←Older revision		Revision as of 00:23, 25 March 2013
Line 1:		Line 1:
-	[[Image:3f66.png\|left\|200px]]
-
	{{STRUCTURE_3f66\| PDB=3f66 \| SCENE= }}		{{STRUCTURE_3f66\| PDB=3f66 \| SCENE= }}
-
	===Human c-Met Kinase in complex with quinoxaline inhibitor===		===Human c-Met Kinase in complex with quinoxaline inhibitor===
-
	{{ABSTRACT_PUBMED_19059779}}		{{ABSTRACT_PUBMED_19059779}}
		+
		+	==Disease==
		+	[[http://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Note=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein. Note=Defects in MET may be associated with gastric cancer. Defects in MET are a cause of hepatocellular carcinoma (HCC) [MIM:[http://omim.org/entry/114550 114550]].<ref>PMID:9927037</ref> Defects in MET are a cause of renal cell carcinoma papillary (RCCP) [MIM:[http://omim.org/entry/605074 605074]]. It is a subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into common renal cell carcinoma (clear cell, non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma.<ref>PMID:9140397</ref><ref>PMID:9563489</ref><ref>PMID:10433944</ref><ref>PMID:10417759</ref><ref>PMID:10327054</ref> Note=A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes. Note=MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies.<ref>PMID:20949619</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/MET_HUMAN MET_HUMAN]] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells.<ref>PMID:1846706</ref><ref>PMID:8182137</ref><ref>PMID:15314156</ref> Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.<ref>PMID:1846706</ref><ref>PMID:8182137</ref><ref>PMID:15314156</ref>

	==About this Structure==		==About this Structure==
	[[3f66]] is a 2 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=3F66 OCA].		[[3f66]] is a 2 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=3F66 OCA].
		+
		+	==See Also==
		+	*[[Hepatocyte growth factor receptor\|Hepatocyte growth factor receptor]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:019059779</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019059779</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]

OCA: Protected "3f66" [edit=sysop:move=sysop]

2013-02-13T10:53:33Z

Protected "3f66" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:53, 13 February 2013

OCA at 10:53, 13 February 2013

2013-02-13T10:53:31Z

←Older revision		Revision as of 10:53, 13 February 2013
Line 1:		Line 1:
-	{{Seed}}
	[[Image:3f66.png\|left\|200px]]		[[Image:3f66.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3f66", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3f66\| PDB=3f66 \| SCENE= }}		{{STRUCTURE_3f66\| PDB=3f66 \| SCENE= }}

	===Human c-Met Kinase in complex with quinoxaline inhibitor===		===Human c-Met Kinase in complex with quinoxaline inhibitor===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19059779}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19059779 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_19059779}}		{{ABSTRACT_PUBMED_19059779}}
-
-	==Disease==
-	Known disease associated with this structure: Hepatocellular carcinoma, childhood type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164860 164860]], Renal cell carcinoma, papillary, familial and sporadic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164860 164860]], Autism, suseptibility to, 9 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164860 164860]]

	==About this Structure==		==About this Structure==
-	~~3F66~~ is a 2 ~~chains~~ structure ~~of sequences~~ 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=3F66 OCA].	+	[[3f66]] is a 2 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=3F66 OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19059779~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019059779</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
Line 51:		Line 36:
	[[Category: Transmembrane]]		[[Category: Transmembrane]]
	[[Category: Tyrosine-protein kinase.]]		[[Category: Tyrosine-protein kinase.]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Sep 21 20:14:22 2009''

OCA at 17:14, 21 September 2009

2009-09-21T17:14:23Z

←Older revision		Revision as of 17:14, 21 September 2009
Line 23:		Line 23:

	==About this Structure==		==About this Structure==
-	3F66 is a ~~[[Single protein]]~~ structure of ~~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=3F66 OCA].	+	3F66 is a 2 chains structure of sequences 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=3F66 OCA].

	==Reference==		==Reference==
-	Discovery of a novel series of quinoxalines as inhibitors of c-Met kinase., Porter J, Lumb S, Lecomte F, Reuberson J, Foley A, Calmiano M, le Riche K, Edwards H, Delgado J, Franklin RJ, Gascon-Simorte JM, Maloney A, Meier C, Batchelor M, Bioorg Med Chem Lett. 2008 Nov 21. PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/19059779 19059779]~~	+	<ref group="xtra">PMID:19059779</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: ~~Single protein~~]]	+	[[Category: Ceska, T.]]
-	[[Category: ~~Pdbx_ordinal=~~, ~~<PDBx:audit_author~~.]]	+	[[Category: Meier, C.]]
	[[Category: Alternative splicing]]		[[Category: Alternative splicing]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
Line 52:		Line 52:
	[[Category: Tyrosine-protein kinase.]]		[[Category: Tyrosine-protein kinase.]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed Jan 7~~ 20:11:06 2009''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Sep 21 20:14:22 2009''

OCA at 17:41, 8 January 2009

2009-01-08T17:41:34Z

←Older revision		Revision as of 17:41, 8 January 2009
Line 23:		Line 23:

	==About this Structure==		==About this Structure==
-	3F66 is a ~~2 chains~~ structure of ~~sequences~~ 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=3F66 OCA].	+	3F66 is a [[Single protein]] structure of 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=3F66 OCA].

	==Reference==		==Reference==
Line 29:		Line 29:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: ~~Ceska, T.~~]]	+	[[Category: Single protein]]
-	[[Category: ~~Meier~~, C.]]	+	[[Category: Pdbx_ordinal=, <PDBx:audit_author.]]
	[[Category: Alternative splicing]]		[[Category: Alternative splicing]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
Line 52:		Line 52:
	[[Category: Tyrosine-protein kinase.]]		[[Category: Tyrosine-protein kinase.]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 7 08:17:51 2009''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 7 20:11:06 2009''