2qi8 - Revision history

OCA at 09:16, 21 February 2024

OCA — Wed, 21 Feb 2024 09:16:25 GMT

←Older revision		Revision as of 09:16, 21 February 2024
Line 3:		Line 3:
	<StructureSection load='2qi8' size='340' side='right'caption='[[2qi8]], [[Resolution\|resolution]] 2.32Å' scene=''>		<StructureSection load='2qi8' size='340' side='right'caption='[[2qi8]], [[Resolution\|resolution]] 2.32Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2qi8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Chick Chick~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QI8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2qi8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QI8 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.32Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>SRC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id=~~9031 CHICK])</td~~><~~/tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>~~[https://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2]~~ </~~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=2qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi8 OCA], [https://pdbe.org/2qi8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qi8 RCSB], [https://www.ebi.ac.uk/pdbsum/2qi8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qi8 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=2qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi8 OCA], [https://pdbe.org/2qi8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qi8 RCSB], [https://www.ebi.ac.uk/pdbsum/2qi8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qi8 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/SRC_CHICK SRC_CHICK]] Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process. When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus.<ref>PMID:1717492</ref> <ref>PMID:8550628</ref>	+	[https://www.uniprot.org/uniprot/SRC_CHICK SRC_CHICK] Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process. When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus.<ref>PMID:1717492</ref> <ref>PMID:8550628</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</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=2qi8 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=2qi8 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Resistance to kinase-targeted cancer drugs has recently been linked to a single point mutation in the ATP binding site of the kinase. In EGFR, the crucial Thr790 gatekeeper residue is mutated to a Met and prevents reversible ATP competitive inhibitors from binding. Irreversible 4-(phenylamino)quinazolines have been shown to overcome this drug resistance and are currently in clinical trials. In order to obtain a detailed structural understanding of how irreversible inhibitors overcome drug resistance, we used Src kinase as a model system for drug resistant EGFR-T790M. We report the first crystal structure of a drug resistant kinase in complex with an irreversible inhibitor. This 4-(phenylamino)quinazoline inhibits wild type and drug resistant EGFR in vitro at low nM concentrations. The co-crystal structure of drug resistant cSrc-T338M kinase domain provides the structural basis of this activity.
-
-	Structural insights into how irreversible inhibitors can overcome drug resistance in EGFR.,Michalczyk A, Kluter S, Rode HB, Simard JR, Grutter C, Rabiller M, Rauh D Bioorg Med Chem. 2008 Apr 1;16(7):3482-8. Epub 2008 Feb 20. PMID:18316192<ref>PMID:18316192</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 2qi8" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Chick~~]]	+	[[Category: Gallus gallus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific protein-tyrosine kinase]]~~	+	[[Category: Gruetter C]]
-	[[Category: Gruetter, C]]	+	[[Category: Michalczyk A]]
-	[[Category: Michalczyk, A]]	+	[[Category: Rauh D]]
-	[[Category: Rauh, D]]	+	[[Category: Rode HB]]
-	[[Category: Rode~~, H B]]~~	+
-	~~[[Category: Drug resistance]]~~	+
-	~~[[Category: Signaling protein]]~~	+
-	~~[[Category: Src kinase domain]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 08:20, 25 June 2021

OCA — Fri, 25 Jun 2021 08:20:55 GMT

←Older revision		Revision as of 08:20, 25 June 2021
Line 1:		Line 1:

	==Crystal structure of drug resistant SRC kinase domain==		==Crystal structure of drug resistant SRC kinase domain==
-	<StructureSection load='2qi8' size='340' side='right' caption='[[2qi8]], [[Resolution\|resolution]] 2.32Å' scene=''>	+	<StructureSection load='2qi8' size='340' side='right'caption='[[2qi8]], [[Resolution\|resolution]] 2.32Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2qi8]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Chick Chick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI8 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2QI8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2qi8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chick Chick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QI8 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SRC ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SRC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi8 OCA], [~~http~~://pdbe.org/2qi8 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2qi8 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2qi8 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2qi8 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=2qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi8 OCA], [https://pdbe.org/2qi8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qi8 RCSB], [https://www.ebi.ac.uk/pdbsum/2qi8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qi8 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/SRC_CHICK SRC_CHICK]] Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process. When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus.<ref>PMID:1717492</ref> <ref>PMID:8550628</ref>	+	[[https://www.uniprot.org/uniprot/SRC_CHICK SRC_CHICK]] Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process. When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus.<ref>PMID:1717492</ref> <ref>PMID:8550628</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 32:		Line 32:

	==See Also==		==See Also==
-	*[[Tyrosine kinase\|Tyrosine kinase]]	+	*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Chick]]		[[Category: Chick]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Gruetter, C]]		[[Category: Gruetter, C]]

OCA at 11:05, 5 September 2018

OCA — Wed, 05 Sep 2018 11:05:54 GMT

←Older revision		Revision as of 11:05, 5 September 2018
Line 1:		Line 1:
		+
	==Crystal structure of drug resistant SRC kinase domain==		==Crystal structure of drug resistant SRC kinase domain==
	<StructureSection load='2qi8' size='340' side='right' caption='[[2qi8]], [[Resolution\|resolution]] 2.32Å' scene=''>		<StructureSection load='2qi8' size='340' side='right' caption='[[2qi8]], [[Resolution\|resolution]] 2.32Å' scene=''>
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	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi8 OCA], [http://pdbe.org/2qi8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qi8 RCSB], [http://www.ebi.ac.uk/pdbsum/2qi8 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=2qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi8 OCA], [http://pdbe.org/2qi8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qi8 RCSB], [http://www.ebi.ac.uk/pdbsum/2qi8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2qi8 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 14:		Line 15:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qi/2qi8_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qi/2qi8_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 01:29, 10 February 2016

OCA — Wed, 10 Feb 2016 01:29:03 GMT

←Older revision		Revision as of 01:29, 10 February 2016
Line 18:		Line 18:
	<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=2qi8 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 04:01, 11 September 2015

OCA — Fri, 11 Sep 2015 04:01:12 GMT

←Older revision		Revision as of 04:01, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='2qi8' size='340' side='right' caption='[[2qi8]], [[Resolution\|resolution]] 2.32Å' scene=''>		<StructureSection load='2qi8' size='340' side='right' caption='[[2qi8]], [[Resolution\|resolution]] 2.32Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2qi8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Gallus_gallus Gallus gallus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QI8 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2qi8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Chick Chick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QI8 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 ~~Gallus gallus~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2qi8 RCSB], [http://www.ebi.ac.uk/pdbsum/2qi8 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=2qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi8 OCA], [http://pdbe.org/2qi8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qi8 RCSB], [http://www.ebi.ac.uk/pdbsum/2qi8 PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 28:		Line 28:
	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 2qi8" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 35:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Gallus gallus~~]]	+	[[Category: Chick]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Gruetter, C]]		[[Category: Gruetter, C]]

OCA at 10:51, 25 December 2014

OCA — Thu, 25 Dec 2014 10:51:15 GMT

←Older revision		Revision as of 10:51, 25 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2qi8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QI8 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2qi8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QI8 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 Gallus gallus])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 Gallus gallus])</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2qi8 RCSB], [http://www.ebi.ac.uk/pdbsum/2qi8 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=2qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2qi8 RCSB], [http://www.ebi.ac.uk/pdbsum/2qi8 PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/SRC_CHICK SRC_CHICK]] Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process. When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus.<ref>PMID:1717492</ref> <ref>PMID:8550628</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 35:		Line 37:
	[[Category: Gallus gallus]]		[[Category: Gallus gallus]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
-	[[Category: Gruetter, C.]]	+	[[Category: Gruetter, C]]
-	[[Category: Michalczyk, A.]]	+	[[Category: Michalczyk, A]]
-	[[Category: Rauh, D.]]	+	[[Category: Rauh, D]]
-	[[Category: Rode, H B.]]	+	[[Category: Rode, H B]]
	[[Category: Drug resistance]]		[[Category: Drug resistance]]
	[[Category: Signaling protein]]		[[Category: Signaling protein]]
	[[Category: Src kinase domain]]		[[Category: Src kinase domain]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 09:52, 29 September 2014

OCA — Mon, 29 Sep 2014 09:52:51 GMT

←Older revision		Revision as of 09:52, 29 September 2014
Line 1:		Line 1:
-	[[~~Image:~~2qi8.~~png~~\|~~left~~\|200px]]	+	==Crystal structure of drug resistant SRC kinase domain==
		+	<StructureSection load='2qi8' size='340' side='right' caption='[[2qi8]], [[Resolution\|resolution]] 2.32Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2qi8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QI8 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 Gallus gallus])</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2qi8 RCSB], [http://www.ebi.ac.uk/pdbsum/2qi8 PDBsum]</span></td></tr>
		+	<table>
		+	== 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/qi/2qi8_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 ==
		+	Resistance to kinase-targeted cancer drugs has recently been linked to a single point mutation in the ATP binding site of the kinase. In EGFR, the crucial Thr790 gatekeeper residue is mutated to a Met and prevents reversible ATP competitive inhibitors from binding. Irreversible 4-(phenylamino)quinazolines have been shown to overcome this drug resistance and are currently in clinical trials. In order to obtain a detailed structural understanding of how irreversible inhibitors overcome drug resistance, we used Src kinase as a model system for drug resistant EGFR-T790M. We report the first crystal structure of a drug resistant kinase in complex with an irreversible inhibitor. This 4-(phenylamino)quinazoline inhibits wild type and drug resistant EGFR in vitro at low nM concentrations. The co-crystal structure of drug resistant cSrc-T338M kinase domain provides the structural basis of this activity.

-	~~{{STRUCTURE_2qi8\| PDB=2qi8 \| SCENE= }}~~	+	Structural insights into how irreversible inhibitors can overcome drug resistance in EGFR.,Michalczyk A, Kluter S, Rode HB, Simard JR, Grutter C, Rabiller M, Rauh D Bioorg Med Chem. 2008 Apr 1;16(7):3482-8. Epub 2008 Feb 20. PMID:18316192<ref>PMID:18316192</ref>

-	~~===Crystal structure~~ of ~~drug resistant SRC kinase domain===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_18316192}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[2qi8]] is a 2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Gallus_gallus Gallus gallus]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=2QI8 OCA].~~	+

	==See Also==		==See Also==
-	*[[~~Proto-oncogene tyrosine-protein~~ kinase\|~~Proto-oncogene tyrosine-protein~~ kinase]]	+	*[[Tyrosine kinase\|Tyrosine kinase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:018316192<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Gallus gallus]]		[[Category: Gallus gallus]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]

OCA at 15:50, 20 October 2012

OCA — Sat, 20 Oct 2012 15:50:21 GMT

←Older revision		Revision as of 15:50, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[2qi8]] is a 2 chain structure ~~of [[Proto-oncogene tyrosine-protein kinase]]~~ with sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI8 OCA].	+	[[2qi8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI8 OCA].

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

OCA: Protected "2qi8" [edit=sysop:move=sysop]

OCA — Thu, 26 Jul 2012 19:40:01 GMT

Protected "2qi8" [edit=sysop:move=sysop]

←Older revision

Revision as of 19:40, 26 July 2012

OCA at 19:39, 26 July 2012

OCA — Thu, 26 Jul 2012 19:39:59 GMT

←Older revision		Revision as of 19:39, 26 July 2012
Line 1:		Line 1:
-	{{Seed}}
	[[Image:2qi8.png\|left\|200px]]		[[Image:2qi8.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_2qi8", 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_2qi8\| PDB=2qi8 \| SCENE= }}		{{STRUCTURE_2qi8\| PDB=2qi8 \| SCENE= }}

	===Crystal structure of drug resistant SRC kinase domain===		===Crystal structure of drug resistant SRC kinase domain===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_18316192}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 18316192 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_18316192}}		{{ABSTRACT_PUBMED_18316192}}

	==About this Structure==		==About this Structure==
-	~~2QI8~~ is a 2 ~~chains~~ structure of ~~sequences~~ from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI8 OCA].	+	[[2qi8]] is a 2 chain structure of [[Proto-oncogene tyrosine-protein kinase]] with sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QI8 OCA].
		+
		+	==See Also==
		+	*[[Proto-oncogene tyrosine-protein kinase\|Proto-oncogene tyrosine-protein kinase]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~18316192~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:018316192</ref><references group="xtra"/>
	[[Category: Gallus gallus]]		[[Category: Gallus gallus]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
Line 34:		Line 25:
	[[Category: Src kinase domain]]		[[Category: Src kinase domain]]
	[[Category: Transferase]]		[[Category: Transferase]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 14:19:20 2009''