5tc0 - Revision history

OCA at 14:20, 6 March 2024

2024-03-06T14:20:13Z

←Older revision		Revision as of 14:20, 6 March 2024
Line 3:		Line 3:
	<StructureSection load='5tc0' size='340' side='right'caption='[[5tc0]], [[Resolution\|resolution]] 2.24Å' scene=''>		<StructureSection load='5tc0' size='340' side='right'caption='[[5tc0]], [[Resolution\|resolution]] 2.24Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5tc0]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TC0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5TC0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5tc0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TC0 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=79Y:N-(2-{4~~-[~~(2S)-4-(METHYLSULFONYL)MORPHOLIN-2-YL~~]~~-1,3-THIAZOL-~~2~~-YL}PHENYL)-1H-IMIDAZOLE-2-CARBOXAMIDE'>79Y</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]] 2.24Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>MERTK, MER ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=79Y:N-(2-{4-[(2S)-4-(METHYLSULFONYL)MORPHOLIN-2-YL]-1,3-THIAZOL-2-YL}PHENYL)-1H-IMIDAZOLE-2-CARBOXAMIDE'>79Y</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5tc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tc0 OCA], [https://pdbe.org/5tc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tc0 RCSB], [https://www.ebi.ac.uk/pdbsum/5tc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tc0 ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5tc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tc0 OCA], [~~http~~://pdbe.org/5tc0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5tc0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5tc0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5tc0 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/MERTK_HUMAN MERTK_HUMAN]] Defects in MERTK are the cause of retinitis pigmentosa type 38 (RP38) [MIM:[~~http~~://omim.org/entry/613862 613862]]. RP38 is a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.<ref>PMID:11062461</ref>	+	[https://www.uniprot.org/uniprot/MERTK_HUMAN MERTK_HUMAN] Defects in MERTK are the cause of retinitis pigmentosa type 38 (RP38) [MIM:[https://omim.org/entry/613862 613862]. RP38 is a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.<ref>PMID:11062461</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/MERTK_HUMAN MERTK_HUMAN]] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.<ref>PMID:17005688</ref>	+	[https://www.uniprot.org/uniprot/MERTK_HUMAN MERTK_HUMAN] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.<ref>PMID:17005688</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Axl has been a target of interest in the oncology field for several years based on its role in various oncogenic processes. To date, no wild-type Axl crystal structure has been reported. Herein, we describe the structure-based optimization of a novel chemotype of Axl inhibitors, 1H-imidazole-2-carboxamide, using a mutated kinase homolog, Mer(I650M), as a crystallographic surrogate. Iterative optimization of the initial lead compound (1) led to compound (21), a selective and potent inhibitor of wild-type Axl. Compound (21) will serve as a useful compound for further in vivo studies.	+
-		+
-	Structure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate.,Keung W, Boloor A, Brown J, Kiryanov A, Gangloff A, Lawson JD, Skene R, Hoffman I, Atienza J, Kahana J, De Jong R, Farrell P, Balakrishna D, Halkowycz P Bioorg Med Chem Lett. 2016 Dec 20. pii: S0960-894X(16)31291-4. doi:, 10.1016/j.bmcl.2016.12.024. PMID:28082036<ref>PMID:28082036</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5tc0" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 29:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein-tyrosine kinase]]~~	+	[[Category: Hoffman ID]]
-	[[Category: Hoffman~~, I D~~]]	+	[[Category: Lawson JD]]
-	[[Category: Lawson~~, J D]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Oncology]]~~	+
-	~~[[Category: Surrogate]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 11:28, 16 September 2020

2020-09-16T11:28:51Z

←Older revision		Revision as of 11:28, 16 September 2020
Line 1:		Line 1:

	==Structure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate==		==Structure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate==
-	<StructureSection load='5tc0' size='340' side='right' caption='[[5tc0]], [[Resolution\|resolution]] 2.24Å' scene=''>	+	<StructureSection load='5tc0' size='340' side='right'caption='[[5tc0]], [[Resolution\|resolution]] 2.24Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5tc0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TC0 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5TC0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5tc0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TC0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5TC0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=79Y:N-(2-{4-[(2S)-4-(METHYLSULFONYL)MORPHOLIN-2-YL]-1,3-THIAZOL-2-YL}PHENYL)-1H-IMIDAZOLE-2-CARBOXAMIDE'>79Y</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=79Y:N-(2-{4-[(2S)-4-(METHYLSULFONYL)MORPHOLIN-2-YL]-1,3-THIAZOL-2-YL}PHENYL)-1H-IMIDAZOLE-2-CARBOXAMIDE'>79Y</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MERTK, MER ([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=5tc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tc0 OCA], [http://pdbe.org/5tc0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tc0 RCSB], [http://www.ebi.ac.uk/pdbsum/5tc0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tc0 ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5tc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tc0 OCA], [http://pdbe.org/5tc0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tc0 RCSB], [http://www.ebi.ac.uk/pdbsum/5tc0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tc0 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5tc0" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5tc0" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Hoffman, I D]]		[[Category: Hoffman, I D]]

OCA at 23:33, 25 January 2017

2017-01-25T23:33:53Z

←Older revision		Revision as of 23:33, 25 January 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5tc0 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate==
		+	<StructureSection load='5tc0' size='340' side='right' caption='[[5tc0]], [[Resolution\|resolution]] 2.24Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5tc0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TC0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TC0 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=79Y:N-(2-{4-[(2S)-4-(METHYLSULFONYL)MORPHOLIN-2-YL]-1,3-THIAZOL-2-YL}PHENYL)-1H-IMIDAZOLE-2-CARBOXAMIDE'>79Y</scene></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=5tc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tc0 OCA], [http://pdbe.org/5tc0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tc0 RCSB], [http://www.ebi.ac.uk/pdbsum/5tc0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tc0 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/MERTK_HUMAN MERTK_HUMAN]] Defects in MERTK are the cause of retinitis pigmentosa type 38 (RP38) [MIM:[http://omim.org/entry/613862 613862]]. RP38 is a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.<ref>PMID:11062461</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/MERTK_HUMAN MERTK_HUMAN]] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6. Regulates many physiological processes including cell survival, migration, differentiation, and phagocytosis of apoptotic cells (efferocytosis). Ligand binding at the cell surface induces autophosphorylation of MERTK on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with GRB2 or PLCG2 and induces phosphorylation of MAPK1, MAPK2, FAK/PTK2 or RAC1. MERTK signaling plays a role in various processes such as macrophage clearance of apoptotic cells, platelet aggregation, cytoskeleton reorganization and engulfment. Functions in the retinal pigment epithelium (RPE) as a regulator of rod outer segments fragments phagocytosis. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3.<ref>PMID:17005688</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Axl has been a target of interest in the oncology field for several years based on its role in various oncogenic processes. To date, no wild-type Axl crystal structure has been reported. Herein, we describe the structure-based optimization of a novel chemotype of Axl inhibitors, 1H-imidazole-2-carboxamide, using a mutated kinase homolog, Mer(I650M), as a crystallographic surrogate. Iterative optimization of the initial lead compound (1) led to compound (21), a selective and potent inhibitor of wild-type Axl. Compound (21) will serve as a useful compound for further in vivo studies.

-	~~Authors~~:	+	Structure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate.,Keung W, Boloor A, Brown J, Kiryanov A, Gangloff A, Lawson JD, Skene R, Hoffman I, Atienza J, Kahana J, De Jong R, Farrell P, Balakrishna D, Halkowycz P Bioorg Med Chem Lett. 2016 Dec 20. pii: S0960-894X(16)31291-4. doi:, 10.1016/j.bmcl.2016.12.024. PMID:28082036<ref>PMID:28082036</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5tc0" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Receptor protein-tyrosine kinase]]
		+	[[Category: Hoffman, I D]]
		+	[[Category: Lawson, J D]]
		+	[[Category: Inhibitor]]
		+	[[Category: Kinase]]
		+	[[Category: Oncology]]
		+	[[Category: Surrogate]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 19:53, 5 October 2016

2016-10-05T19:53:54Z

←Older revision		Revision as of 19:53, 5 October 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5tc0 is ON HOLD	+	The entry 5tc0 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "5tc0" [edit=sysop:move=sysop]

2016-09-21T12:29:06Z

Protected "5tc0" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:29, 21 September 2016

OCA: New page: '''Unreleased structure''' The entry 5tc0 is ON HOLD Authors: Description: Category: Unreleased Structures

2016-09-21T12:29:05Z

New page: '''Unreleased structure''' The entry 5tc0 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5tc0 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]