3q6w - Revision history

OCA at 05:54, 8 June 2022

OCA — Wed, 08 Jun 2022 05:54:13 GMT

←Older revision		Revision as of 05:54, 8 June 2022
Line 1:		Line 1:

	==Structure of dually-phosphorylated MET receptor kinase in complex with an MK-2461 analog with specificity for the activated receptor==		==Structure of dually-phosphorylated MET receptor kinase in complex with an MK-2461 analog with specificity for the activated receptor==
-	<StructureSection load='3q6w' size='340' side='right' caption='[[3q6w]], [[Resolution\|resolution]] 1.75Å' scene=''>	+	<StructureSection load='3q6w' size='340' side='right'caption='[[3q6w]], [[Resolution\|resolution]] 1.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3q6w]] 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=3Q6W OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3Q6W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3q6w]] 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=3Q6W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q6W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Q6W:3-{5-OXO-3-[1-(PIPERIDIN-4-YL)-1H-PYRAZOL-4-YL]-5H-BENZO[4,5]CYCLOHEPTA[1,2-B]PYRIDIN-7-YL}-N-(PYRIDIN-2-YLMETHYL)PROPANAMIDE'>Q6W</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Q6W:3-{5-OXO-3-[1-(PIPERIDIN-4-YL)-1H-PYRAZOL-4-YL]-5H-BENZO[4,5]CYCLOHEPTA[1,2-B]PYRIDIN-7-YL}-N-(PYRIDIN-2-YLMETHYL)PROPANAMIDE'>Q6W</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3q6u\|3q6u]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3q6u\|3q6u]]</div></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=3q6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q6w OCA], [~~http~~://pdbe.org/3q6w PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3q6w RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3q6w PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3q6w 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=3q6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q6w OCA], [https://pdbe.org/3q6w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q6w RCSB], [https://www.ebi.ac.uk/pdbsum/3q6w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q6w 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 24:
	</div>		</div>
	<div class="pdbe-citations 3q6w" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3q6w" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Hepatocyte growth factor receptor 3D structures\|Hepatocyte growth factor receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 32:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Lumb, K J]]		[[Category: Lumb, K J]]

OCA at 09:11, 8 November 2017

OCA — Wed, 08 Nov 2017 09:11:49 GMT

←Older revision		Revision as of 09:11, 8 November 2017
Line 24:		Line 24:
	</div>		</div>
	<div class="pdbe-citations 3q6w" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3q6w" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Hepatocyte growth factor receptor\|Hepatocyte growth factor receptor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 01:51, 5 August 2016

OCA — Fri, 05 Aug 2016 01:51:37 GMT

←Older revision		Revision as of 01:51, 5 August 2016
Line 1:		Line 1:
		+
	==Structure of dually-phosphorylated MET receptor kinase in complex with an MK-2461 analog with specificity for the activated receptor==		==Structure of dually-phosphorylated MET receptor kinase in complex with an MK-2461 analog with specificity for the activated receptor==
	<StructureSection load='3q6w' size='340' side='right' caption='[[3q6w]], [[Resolution\|resolution]] 1.75Å' scene=''>		<StructureSection load='3q6w' size='340' side='right' caption='[[3q6w]], [[Resolution\|resolution]] 1.75Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3q6w]] 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=3Q6W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q6W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3q6w]] 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=3Q6W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q6W FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Q6W:3-{5-OXO-3-[1-(PIPERIDIN-4-YL)-1H-PYRAZOL-4-YL]-5H-BENZO[4,5]CYCLOHEPTA[1,2-B]PYRIDIN-7-YL}-N-(PYRIDIN-2-YLMETHYL)PROPANAMIDE'>Q6W</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Q6W:3-{5-OXO-3-[1-(PIPERIDIN-4-YL)-1H-PYRAZOL-4-YL]-5H-BENZO[4,5]CYCLOHEPTA[1,2-B]PYRIDIN-7-YL}-N-(PYRIDIN-2-YLMETHYL)PROPANAMIDE'>Q6W</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3q6u\|3q6u]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3q6u\|3q6u]]</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=3q6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q6w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q6w RCSB], [http://www.ebi.ac.uk/pdbsum/3q6w 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=3q6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q6w OCA], [http://pdbe.org/3q6w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3q6w RCSB], [http://www.ebi.ac.uk/pdbsum/3q6w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3q6w ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 22:		Line 23:
	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 3q6w" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 29:		Line 31:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Lumb, K J]]		[[Category: Lumb, K J]]

OCA at 10:36, 19 December 2014

OCA — Fri, 19 Dec 2014 10:36:27 GMT

←Older revision		Revision as of 10:36, 19 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3q6w\| PDB=3q6w \| SCENE= }}~~	+	==Structure of dually-phosphorylated MET receptor kinase in complex with an MK-2461 analog with specificity for the activated receptor==
-	===Structure of dually-phosphorylated MET receptor kinase in complex with an MK-2461 analog with specificity for the activated receptor===	+	<StructureSection load='3q6w' size='340' side='right' caption='[[3q6w]], [[Resolution\|resolution]] 1.75Å' scene=''>
-	{~~{ABSTRACT_PUBMED_21247903}~~}	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3q6w]] 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=3Q6W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q6W FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Q6W:3-{5-OXO-3-[1-(PIPERIDIN-4-YL)-1H-PYRAZOL-4-YL]-5H-BENZO[4,5]CYCLOHEPTA[1,2-B]PYRIDIN-7-YL}-N-(PYRIDIN-2-YLMETHYL)PROPANAMIDE'>Q6W</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3q6u\|3q6u]]</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=3q6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q6w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q6w RCSB], [http://www.ebi.ac.uk/pdbsum/3q6w 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The receptor tyrosine kinase c-Met is implicated in oncogenesis and is the target for several small molecule and biologic agents in clinical trials for the treatment of cancer. Binding of the hepatocyte growth factor to the cell surface receptor of c-Met induces activation via autophosphorylation of the kinase domain. Here we describe the structural basis of c-Met activation upon autophosphorylation and the selective small molecule inhibiton of autophosphorylated c-Met. MK-2461 is a potent c-Met inhibitor that is selective for the phosphorylated state of the enzyme. Compound 1 is an MK-2461 analog with a 20-fold enthalpy-driven preference for the autophosphorylated over unphosphorylated c-Met kinase domain. The crystal structure of the unbound kinase domain phosphorylated at Tyr-1234 and Tyr-1235 shows that activation loop phosphorylation leads to the ejection and disorder of the activation loop and rearrangement of helix alphaC and the G loop to generate a viable active site. Helix alphaC adopts a orientation different from that seen in activation loop mutants. The crystal structure of the complex formed by the autophosphorylated c-Met kinase domain and compound 1 reveals a significant induced fit conformational change of the G loop and ordering of the activation loop, explaining the selectivity of compound 1 for the autophosphorylated state. The results highlight the role of structural plasticity within the kinase domain in imparting the specificity of ligand binding and provide the framework for structure-guided design of activated c-Met inhibitors.

-	~~==Disease==~~	+	Structural basis for selective small molecule kinase inhibition of activated c-Met.,Rickert KW, Patel SB, Allison TJ, Byrne NJ, Darke PL, Ford RE, Guerin DJ, Hall DL, Kornienko M, Lu J, Munshi SK, Reid JC, Shipman JM, Stanton EF, Wilson KJ, Young JR, Soisson SM, Lumb KJ J Biol Chem. 2011 Apr 1;286(13):11218-25. Epub 2011 Jan 18. PMID:21247903<ref>PMID:21247903</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==~~	+
-	[[3q6w]] 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=3Q6W 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:021247903</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: Lumb, K J.]]	+	[[Category: Lumb, K J]]
-	[[Category: Patel, S B.]]	+	[[Category: Patel, S B]]
-	[[Category: Rickert, K W.]]	+	[[Category: Rickert, K W]]
-	[[Category: Soisson, S M.]]	+	[[Category: Soisson, S M]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]
	[[Category: Two phosphotyrosine resiude]]		[[Category: Two phosphotyrosine resiude]]
	[[Category: Tyrosine kinase]]		[[Category: Tyrosine kinase]]

OCA at 06:48, 25 March 2013

OCA — Mon, 25 Mar 2013 06:48:45 GMT

←Older revision		Revision as of 06:48, 25 March 2013
Line 1:		Line 1:
-	[[Image:3q6w.png\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3q6w", 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_3q6w\| PDB=3q6w \| SCENE= }}		{{STRUCTURE_3q6w\| PDB=3q6w \| SCENE= }}
-
	===Structure of dually-phosphorylated MET receptor kinase in complex with an MK-2461 analog with specificity for the activated receptor===		===Structure of dually-phosphorylated MET receptor kinase in complex with an MK-2461 analog with specificity for the activated receptor===
		+	{{ABSTRACT_PUBMED_21247903}}

		+	==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==
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_21247903}}, adds the Publication Abstract to the page~~	+	[[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>
-	~~(as it appears on PubMed at~~ http://www.~~pubmed~~.~~gov)~~, ~~where 21247903 is~~ the ~~PubMed ID number~~.	+
-	-->	+
-	~~{{ABSTRACT_PUBMED_21247903}}~~	+

	==About this Structure==		==About this Structure==
	[[3q6w]] 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=3Q6W OCA].		[[3q6w]] 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=3Q6W OCA].
		+
		+	==See Also==
		+	*[[Hepatocyte growth factor receptor\|Hepatocyte growth factor receptor]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:021247903</ref><references group="xtra"/>	+	<ref group="xtra">PMID:021247903</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]

OCA at 16:00, 22 June 2011

OCA — Wed, 22 Jun 2011 16:00:31 GMT

←Older revision		Revision as of 16:00, 22 June 2011
Line 1:		Line 1:
-	[[Image:3q6w.~~jpg~~\|left\|200px]]	+	[[Image:3q6w.png\|left\|200px]]

	<!--		<!--
Line 11:		Line 11:
	===Structure of dually-phosphorylated MET receptor kinase in complex with an MK-2461 analog with specificity for the activated receptor===		===Structure of dually-phosphorylated MET receptor kinase in complex with an MK-2461 analog with specificity for the activated receptor===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21247903}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21247903 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21247903}}

	==About this Structure==		==About this Structure==
	[[3q6w]] 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=3Q6W OCA].		[[3q6w]] 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=3Q6W OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021247903</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
Line 20:		Line 29:
	[[Category: Rickert, K W.]]		[[Category: Rickert, K W.]]
	[[Category: Soisson, S M.]]		[[Category: Soisson, S M.]]
		+	[[Category: Transferase-transferase inhibitor complex]]
		+	[[Category: Two phosphotyrosine resiude]]
		+	[[Category: Tyrosine kinase]]

OCA at 06:30, 19 January 2011

OCA — Wed, 19 Jan 2011 06:30:19 GMT

←Older revision		Revision as of 06:30, 19 January 2011
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3q6w.jpg\|left\|200px]]

-	The ~~entry 3q6w~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3q6w", 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_3q6w\| PDB=3q6w \| SCENE= }}

-	~~Authors: Soisson, S.M., Rickert, K.W., Patel, S.B., Lumb, K.J.~~	+	===Structure of dually-phosphorylated MET receptor kinase in complex with an MK-2461 analog with specificity for the activated receptor===

-	~~Description:~~ Structure ~~of dually-phosphorylated MET receptor kinase in complex~~ with ~~an MK~~-~~2461 analog with specificity for the activated receptor~~	+
		+	==About this Structure==
		+	[[3q6w]] 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=3Q6W OCA].
		+	[[Category: Homo sapiens]]
		+	[[Category: Receptor protein-tyrosine kinase]]
		+	[[Category: Lumb, K J.]]
		+	[[Category: Patel, S B.]]
		+	[[Category: Rickert, K W.]]
		+	[[Category: Soisson, S M.]]

OCA: Protected "3q6w" [edit=sysop:move=sysop]

OCA — Wed, 12 Jan 2011 04:51:19 GMT

Protected "3q6w" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:51, 12 January 2011

OCA: New page: '''Unreleased structure''' The entry 3q6w is ON HOLD Authors: Soisson, S.M., Rickert, K.W., Patel, S.B., Lumb, K.J. Description: Structure of dually-phosphorylated MET receptor kinase ...

OCA — Wed, 12 Jan 2011 04:51:18 GMT

New page: '''Unreleased structure''' The entry 3q6w is ON HOLD Authors: Soisson, S.M., Rickert, K.W., Patel, S.B., Lumb, K.J. Description: Structure of dually-phosphorylated MET receptor kinase ...

New page

'''Unreleased structure'''

The entry 3q6w is ON HOLD

Authors: Soisson, S.M., Rickert, K.W., Patel, S.B., Lumb, K.J.

Description: Structure of dually-phosphorylated MET receptor kinase in complex with an MK-2461 analog with specificity for the activated receptor