5d10 - Revision history

OCA at 11:24, 10 January 2024

OCA — Wed, 10 Jan 2024 11:24:05 GMT

←Older revision		Revision as of 11:24, 10 January 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5d10]] 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=5D10 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5D10 FirstGlance]. <br>		<table><tr><td colspan='2'>[[5d10]] 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=5D10 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5D10 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=563:N-[4-({4-(4-METHYLPIPERAZIN-1-YL)-6-[(5-METHYL-1H-PYRAZOL-3-YL)AMINO]PYRIMIDIN-2-YL}OXY)PHENYL]PROP-2-ENAMIDE'>563</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]] 2.7Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=563:N-[4-({4-(4-METHYLPIPERAZIN-1-YL)-6-[(5-METHYL-1H-PYRAZOL-3-YL)AMINO]PYRIMIDIN-2-YL}OXY)PHENYL]PROP-2-ENAMIDE'>563</scene></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=5d10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d10 OCA], [https://pdbe.org/5d10 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5d10 RCSB], [https://www.ebi.ac.uk/pdbsum/5d10 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5d10 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=5d10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d10 OCA], [https://pdbe.org/5d10 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5d10 RCSB], [https://www.ebi.ac.uk/pdbsum/5d10 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5d10 ProSAT]</span></td></tr>
	</table>		</table>

OCA at 10:17, 21 June 2023

OCA — Wed, 21 Jun 2023 10:17:17 GMT

←Older revision		Revision as of 10:17, 21 June 2023
Line 1:		Line 1:

	==Kinase domain of cSrc in complex with RL236==		==Kinase domain of cSrc in complex with RL236==
-	<StructureSection load='5d10' size='340' side='right' caption='[[5d10]], [[Resolution\|resolution]] 2.70Å' scene=''>	+	<StructureSection load='5d10' size='340' side='right'caption='[[5d10]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5d10]] 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=5D10 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5D10 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5d10]] 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=5D10 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5D10 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=563:N-[4-({4-(4-METHYLPIPERAZIN-1-YL)-6-[(5-METHYL-1H-PYRAZOL-3-YL)AMINO]PYRIMIDIN-2-YL}OXY)PHENYL]PROP-2-ENAMIDE'>563</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=563:N-[4-({4-(4-METHYLPIPERAZIN-1-YL)-6-[(5-METHYL-1H-PYRAZOL-3-YL)AMINO]PYRIMIDIN-2-YL}OXY)PHENYL]PROP-2-ENAMIDE'>563</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5d10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d10 OCA], [https://pdbe.org/5d10 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5d10 RCSB], [https://www.ebi.ac.uk/pdbsum/5d10 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5d10 ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/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=5d10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d10 OCA], [~~http~~://pdbe.org/5d10 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5d10 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5d10 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5d10 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Chick~~]]	+	[[Category: Gallus gallus]]
-	[[Category: ~~Non-specific protein-tyrosine kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Becker, C]]	+	[[Category: Becker C]]
-	[[Category: Julian, E]]	+	[[Category: Julian E]]
-	[[Category: Mayer-Wrangowski~~, S C~~]]	+	[[Category: Mayer-Wrangowski SC]]
-	[[Category: Rauh, D]]	+	[[Category: Rauh D]]
-	~~[[Category: Drug resistance]]~~	+
-	~~[[Category: Kinase inhibitor]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 16:45, 16 November 2017

OCA — Thu, 16 Nov 2017 16:45:05 GMT

←Older revision		Revision as of 16:45, 16 November 2017
Line 1:		Line 1:
		+
	==Kinase domain of cSrc in complex with RL236==		==Kinase domain of cSrc in complex with RL236==
	<StructureSection load='5d10' size='340' side='right' caption='[[5d10]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='5d10' size='340' side='right' caption='[[5d10]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5d10]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D10 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D10 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5d10]] 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=5D10 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D10 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=563:N-[4-({4-(4-METHYLPIPERAZIN-1-YL)-6-[(5-METHYL-1H-PYRAZOL-3-YL)AMINO]PYRIMIDIN-2-YL}OXY)PHENYL]PROP-2-ENAMIDE'>563</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=563:N-[4-({4-(4-METHYLPIPERAZIN-1-YL)-6-[(5-METHYL-1H-PYRAZOL-3-YL)AMINO]PYRIMIDIN-2-YL}OXY)PHENYL]PROP-2-ENAMIDE'>563</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='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=5d10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d10 OCA], [http://pdbe.org/5d10 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d10 RCSB], [http://www.ebi.ac.uk/pdbsum/5d10 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=5d10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d10 OCA], [http://pdbe.org/5d10 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d10 RCSB], [http://www.ebi.ac.uk/pdbsum/5d10 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5d10 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 22:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Chick]]
	[[Category: Non-specific protein-tyrosine kinase]]		[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Becker, C]]		[[Category: Becker, C]]

OCA at 08:16, 30 September 2015

OCA — Wed, 30 Sep 2015 08:16:39 GMT

←Older revision		Revision as of 08:16, 30 September 2015
Line 5:		Line 5:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=563:N-[4-({4-(4-METHYLPIPERAZIN-1-YL)-6-[(5-METHYL-1H-PYRAZOL-3-YL)AMINO]PYRIMIDIN-2-YL}OXY)PHENYL]PROP-2-ENAMIDE'>563</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=563:N-[4-({4-(4-METHYLPIPERAZIN-1-YL)-6-[(5-METHYL-1H-PYRAZOL-3-YL)AMINO]PYRIMIDIN-2-YL}OXY)PHENYL]PROP-2-ENAMIDE'>563</scene></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=5d10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d10 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5d10 RCSB], [http://www.ebi.ac.uk/pdbsum/5d10 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=5d10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d10 OCA], [http://pdbe.org/5d10 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d10 RCSB], [http://www.ebi.ac.uk/pdbsum/5d10 PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 17:
	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 5d10" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 05:08, 9 September 2015

OCA — Wed, 09 Sep 2015 05:08:04 GMT

←Older revision		Revision as of 05:08, 9 September 2015
Line 9:		Line 9:
	== 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>		[[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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Receptor tyrosine kinases represent one of the prime targets in cancer therapy, as the dysregulation of these elementary transducers of extracellular signals, like the epidermal growth factor receptor (EGFR), contributes to the onset of cancer, such as non-small cell lung cancer (NSCLC). Strong efforts were directed to the development of irreversible inhibitors and led to compound CO-1686, which takes advantage of increased residence time at EGFR by alkylating Cys797 and thereby preventing toxic effects. Here, we present a structure-based approach, rationalized by subsequent computational analysis of conformational ligand ensembles in solution, to design novel and irreversible EGFR inhibitors based on a screening hit that was identified in a phenotype screen of 80 NSCLC cell lines against approximately 1500 compounds. Using protein X-ray crystallography, we deciphered the binding mode in engineered cSrc (T338M/S345C), a validated model system for EGFR-T790M, which constituted the basis for further rational design approaches. Chemical synthesis led to further compound collections that revealed increased biochemical potency and, in part, selectivity toward mutated (L858R and L858R/T790M) vs nonmutated EGFR. Further cell-based and kinetic studies were performed to substantiate our initial findings. Utilizing proteolytic digestion and nano-LC-MS/MS analysis, we confirmed the alkylation of Cys797.
		+
		+	Targeting Drug Resistance in EGFR with Covalent Inhibitors: A Structure-Based Design Approach.,Engel J, Richters A, Getlik M, Tomassi S, Keul M, Termathe M, Lategahn J, Becker C, Mayer-Wrangowski S, Grutter C, Uhlenbrock N, Krull J, Schaumann N, Eppmann S, Kibies P, Hoffgaard F, Heil J, Menninger S, Ortiz-Cuaran S, Heuckmann JM, Tinnefeld V, Zahedi RP, Sos ML, Schultz-Fademrecht C, Thomas RK, Kast SM, Rauh D J Med Chem. 2015 Aug 31. PMID:26275028<ref>PMID:26275028</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:35, 2 September 2015

OCA — Wed, 02 Sep 2015 12:35:34 GMT

←Older revision		Revision as of 12:35, 2 September 2015
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==Kinase domain of cSrc in complex with RL236==
-		+	<StructureSection load='5d10' size='340' side='right' caption='[[5d10]], [[Resolution\|resolution]] 2.70Å' scene=''>
-	~~The entry~~ 5d10 is ~~ON HOLD~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5d10]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D10 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D10 FirstGlance]. <br>
-	~~Authors~~: ~~Becker, C~~., ~~Mayer~~-~~Wrangowski~~, S.C.~~, Julian, E~~., ~~Rauh~~, D.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=563:N-[4-({4-(4-METHYLPIPERAZIN-1-YL)-6-[(5-METHYL-1H-PYRAZOL-3-YL)AMINO]PYRIMIDIN-2-YL}OXY)PHENYL]PROP-2-ENAMIDE'>563</scene></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>
-	~~Description: Kinase domain of cSrc in complex with RL236~~	+	<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=5d10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d10 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5d10 RCSB], [http://www.ebi.ac.uk/pdbsum/5d10 PDBsum]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[Category: ~~Rauh, D~~]]	+	== 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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific protein-tyrosine kinase]]
	[[Category: Becker, C]]		[[Category: Becker, C]]
-	[[Category: Mayer-Wrangowski, S.C]]
	[[Category: Julian, E]]		[[Category: Julian, E]]
		+	[[Category: Mayer-Wrangowski, S C]]
		+	[[Category: Rauh, D]]
		+	[[Category: Drug resistance]]
		+	[[Category: Kinase inhibitor]]
		+	[[Category: Transferase]]

OCA: Protected "5d10" [edit=sysop:move=sysop]

OCA — Wed, 12 Aug 2015 13:40:57 GMT

Protected "5d10" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:40, 12 August 2015

OCA: New page: '''Unreleased structure''' The entry 5d10 is ON HOLD Authors: Becker, C., Mayer-Wrangowski, S.C., Julian, E., Rauh, D. Description: Kinase domain of cSrc in complex with RL236 [[Catego...

OCA — Wed, 12 Aug 2015 13:40:55 GMT

New page: '''Unreleased structure''' The entry 5d10 is ON HOLD Authors: Becker, C., Mayer-Wrangowski, S.C., Julian, E., Rauh, D. Description: Kinase domain of cSrc in complex with RL236 [[Catego...

New page

'''Unreleased structure'''

The entry 5d10 is ON HOLD

Authors: Becker, C., Mayer-Wrangowski, S.C., Julian, E., Rauh, D.

Description: Kinase domain of cSrc in complex with RL236
[[Category: Unreleased Structures]]
[[Category: Rauh, D]]
[[Category: Becker, C]]
[[Category: Mayer-Wrangowski, S.C]]
[[Category: Julian, E]]