4rt7 - Revision history

OCA at 08:27, 8 March 2023

OCA — Wed, 08 Mar 2023 08:27:40 GMT

←Older revision		Revision as of 08:27, 8 March 2023
Line 3:		Line 3:
	<StructureSection load='4rt7' size='340' side='right'caption='[[4rt7]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='4rt7' size='340' side='right'caption='[[4rt7]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4rt7]] 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=4RT7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4RT7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4rt7]] is a 1 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=4RT7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RT7 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P30:1-(5-TERT-BUTYL-1,2-OXAZOL-3-YL)-3-(4-{7-[2-(MORPHOLIN-4-YL)ETHOXY]IMIDAZO[2,1-B][1,3]BENZOTHIAZOL-2-YL}PHENYL)UREA'>P30</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P30:1-(5-TERT-BUTYL-1,2-OXAZOL-3-YL)-3-(4-{7-[2-(MORPHOLIN-4-YL)ETHOXY]IMIDAZO[2,1-B][1,3]BENZOTHIAZOL-2-YL}PHENYL)UREA'>P30</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FLT3, CD135, FLK2, STK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4rt7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rt7 OCA], [https://pdbe.org/4rt7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rt7 RCSB], [https://www.ebi.ac.uk/pdbsum/4rt7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rt7 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/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=4rt7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rt7 OCA], [~~http~~://pdbe.org/4rt7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4rt7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4rt7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4rt7 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/FLT3_HUMAN FLT3_HUMAN]] Defects in FLT3 are a cause of acute myelogenous leukemia (AML) [MIM:[~~http~~://omim.org/entry/601626 601626]]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development. Note=Somatic mutations that lead to constitutive activation of FLT3 are frequent in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the activation loop of the kinase domain can result in a constitutively activated kinase.<ref>PMID:11090077</ref> <ref>PMID:16266983</ref> <ref>PMID:14504097</ref> <ref>PMID:9737679</ref> <ref>PMID:18305215</ref> <ref>PMID:11290608</ref> <ref>PMID:8946930</ref> <ref>PMID:11442493</ref>	+	[https://www.uniprot.org/uniprot/FLT3_HUMAN FLT3_HUMAN] Defects in FLT3 are a cause of acute myelogenous leukemia (AML) [MIM:[https://omim.org/entry/601626 601626]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development. Note=Somatic mutations that lead to constitutive activation of FLT3 are frequent in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the activation loop of the kinase domain can result in a constitutively activated kinase.<ref>PMID:11090077</ref> <ref>PMID:16266983</ref> <ref>PMID:14504097</ref> <ref>PMID:9737679</ref> <ref>PMID:18305215</ref> <ref>PMID:11290608</ref> <ref>PMID:8946930</ref> <ref>PMID:11442493</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/FLT3_HUMAN FLT3_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways.<ref>PMID:7507245</ref> <ref>PMID:10080542</ref> <ref>PMID:11090077</ref> <ref>PMID:16266983</ref> <ref>PMID:16627759</ref> <ref>PMID:18490735</ref> <ref>PMID:20111072</ref> <ref>PMID:21067588</ref> <ref>PMID:21262971</ref> <ref>PMID:21516120</ref> <ref>PMID:14504097</ref>	+	[https://www.uniprot.org/uniprot/FLT3_HUMAN FLT3_HUMAN] Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways.<ref>PMID:7507245</ref> <ref>PMID:10080542</ref> <ref>PMID:11090077</ref> <ref>PMID:16266983</ref> <ref>PMID:16627759</ref> <ref>PMID:18490735</ref> <ref>PMID:20111072</ref> <ref>PMID:21067588</ref> <ref>PMID:21262971</ref> <ref>PMID:21516120</ref> <ref>PMID:14504097</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 22:

	==See Also==		==See Also==
-	*[[Tyrosine kinase\|Tyrosine kinase]]	+	*[[Tyrosine kinase 3D structures\|Tyrosine kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein-tyrosine kinase]]~~	+	[[Category: Zhang C]]
-	[[Category: Zhang, C]]	+	[[Category: Zhang Y]]
-	[[Category: Zhang, Y]]	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase inhibitor]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 10:21, 1 May 2019

OCA — Wed, 01 May 2019 10:21:43 GMT

←Older revision		Revision as of 10:21, 1 May 2019
Line 1:		Line 1:

	==Crystal Structure of FLT3 with a small molecule inhibitor==		==Crystal Structure of FLT3 with a small molecule inhibitor==
-	<StructureSection load='4rt7' size='340' side='right' caption='[[4rt7]], [[Resolution\|resolution]] 3.10Å' scene=''>	+	<StructureSection load='4rt7' size='340' side='right'caption='[[4rt7]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4rt7]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RT7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RT7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4rt7]] 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=4RT7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RT7 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P30:1-(5-TERT-BUTYL-1,2-OXAZOL-3-YL)-3-(4-{7-[2-(MORPHOLIN-4-YL)ETHOXY]IMIDAZO[2,1-B][1,3]BENZOTHIAZOL-2-YL}PHENYL)UREA'>P30</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P30:1-(5-TERT-BUTYL-1,2-OXAZOL-3-YL)-3-(4-{7-[2-(MORPHOLIN-4-YL)ETHOXY]IMIDAZO[2,1-B][1,3]BENZOTHIAZOL-2-YL}PHENYL)UREA'>P30</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">FLT3, CD135, FLK2, STK1 ([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=4rt7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rt7 OCA], [http://pdbe.org/4rt7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rt7 RCSB], [http://www.ebi.ac.uk/pdbsum/4rt7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rt7 ProSAT]</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=4rt7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rt7 OCA], [http://pdbe.org/4rt7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rt7 RCSB], [http://www.ebi.ac.uk/pdbsum/4rt7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rt7 ProSAT]</span></td></tr>
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 4rt7" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4rt7" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tyrosine kinase\|Tyrosine kinase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Zhang, C]]		[[Category: Zhang, C]]

OCA at 17:08, 22 March 2017

OCA — Wed, 22 Mar 2017 17:08:11 GMT

←Older revision		Revision as of 17:08, 22 March 2017
Line 1:		Line 1:
		+
	==Crystal Structure of FLT3 with a small molecule inhibitor==		==Crystal Structure of FLT3 with a small molecule inhibitor==
	<StructureSection load='4rt7' size='340' side='right' caption='[[4rt7]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='4rt7' size='340' side='right' caption='[[4rt7]], [[Resolution\|resolution]] 3.10Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P30:1-(5-TERT-BUTYL-1,2-OXAZOL-3-YL)-3-(4-{7-[2-(MORPHOLIN-4-YL)ETHOXY]IMIDAZO[2,1-B][1,3]BENZOTHIAZOL-2-YL}PHENYL)UREA'>P30</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P30:1-(5-TERT-BUTYL-1,2-OXAZOL-3-YL)-3-(4-{7-[2-(MORPHOLIN-4-YL)ETHOXY]IMIDAZO[2,1-B][1,3]BENZOTHIAZOL-2-YL}PHENYL)UREA'>P30</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='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=4rt7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rt7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rt7 RCSB], [http://www.ebi.ac.uk/pdbsum/4rt7 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=4rt7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rt7 OCA], [http://pdbe.org/4rt7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rt7 RCSB], [http://www.ebi.ac.uk/pdbsum/4rt7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rt7 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	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 4rt7" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:42, 22 April 2015

OCA — Wed, 22 Apr 2015 12:42:31 GMT

←Older revision		Revision as of 12:42, 22 April 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal Structure of FLT3 with a small molecule inhibitor==
		+	<StructureSection load='4rt7' size='340' side='right' caption='[[4rt7]], [[Resolution\|resolution]] 3.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4rt7]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RT7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RT7 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=P30:1-(5-TERT-BUTYL-1,2-OXAZOL-3-YL)-3-(4-{7-[2-(MORPHOLIN-4-YL)ETHOXY]IMIDAZO[2,1-B][1,3]BENZOTHIAZOL-2-YL}PHENYL)UREA'>P30</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=4rt7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rt7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rt7 RCSB], [http://www.ebi.ac.uk/pdbsum/4rt7 PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/FLT3_HUMAN FLT3_HUMAN]] Defects in FLT3 are a cause of acute myelogenous leukemia (AML) [MIM:[http://omim.org/entry/601626 601626]]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development. Note=Somatic mutations that lead to constitutive activation of FLT3 are frequent in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the activation loop of the kinase domain can result in a constitutively activated kinase.<ref>PMID:11090077</ref> <ref>PMID:16266983</ref> <ref>PMID:14504097</ref> <ref>PMID:9737679</ref> <ref>PMID:18305215</ref> <ref>PMID:11290608</ref> <ref>PMID:8946930</ref> <ref>PMID:11442493</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/FLT3_HUMAN FLT3_HUMAN]] Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways.<ref>PMID:7507245</ref> <ref>PMID:10080542</ref> <ref>PMID:11090077</ref> <ref>PMID:16266983</ref> <ref>PMID:16627759</ref> <ref>PMID:18490735</ref> <ref>PMID:20111072</ref> <ref>PMID:21067588</ref> <ref>PMID:21262971</ref> <ref>PMID:21516120</ref> <ref>PMID:14504097</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Tyrosine kinase domain mutations are a common cause of acquired clinical resistance to tyrosine kinase inhibitors (TKIs) used to treat cancer, including the FLT3 inhibitor quizartinib. Mutation of kinase "gatekeeper" residues, which control access to an allosteric pocket adjacent to the ATP-binding site, have been frequently implicated in TKI resistance. The molecular underpinnings of gatekeeper mutation-mediated resistance are incompletely understood. We report the first co-crystal structure of FLT3 with the TKI quizartinib, which demonstrates that quizartinib binding relies on essential edge-to-face aromatic interactions with the gatekeeper F691 residue, and F830 within the highly conserved DFG motif in the activation loop. This reliance makes quizartinib critically vulnerable to gatekeeper and activation loop substitutions while minimizing the impact of mutations elsewhere. Moreover, we identify PLX3397, a novel FLT3 inhibitor that retains activity against the F691L mutant due to a binding mode that depends less vitally on specific interactions with the gatekeeper position.

-	~~The entry 4rt7 is ON HOLD until Paper Publication~~	+	Characterizing and Overriding the Structural Mechanism of the Quizartinib-resistant FLT3 "Gatekeeper" F691L Mutation with PLX3397.,Smith CC, Zhang C, Lin K, Lasater EA, Zhang Y, Massi E, Damon LE, Pendleton M, Bashir A, Sebra RP, Perl AE, Kasarskis A, Shellooe R, Tsang G, Carias H, Powell B, Burton EA, Matusow B, Zhang J, Spevak W, Ibrahim PN, Le MH, Hsu H, Habets GG, West BL, Bollag G, Shah NP Cancer Discov. 2015 Apr 6. pii: CD-15-0060. PMID:25847190<ref>PMID:25847190</ref>

-	~~Authors: Zhang~~, Y.~~, Zhang, C~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description~~: ~~Crystal Structure of FLT3 with a small molecule inhibitor~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Receptor protein-tyrosine kinase]]
		+	[[Category: Zhang, C]]
	[[Category: Zhang, Y]]		[[Category: Zhang, Y]]
-	[[Category: ~~Zhang, C~~]]	+	[[Category: Complex]]
		+	[[Category: Kinase]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase inhibitor]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 17:20, 24 December 2014

OCA — Wed, 24 Dec 2014 17:20:04 GMT

←Older revision		Revision as of 17:20, 24 December 2014
Line 6:		Line 6:

	Description: Crystal Structure of FLT3 with a small molecule inhibitor		Description: Crystal Structure of FLT3 with a small molecule inhibitor
		+	[[Category: Unreleased Structures]]
		+	[[Category: Zhang, Y]]
		+	[[Category: Zhang, C]]

OCA at 06:46, 26 November 2014

OCA — Wed, 26 Nov 2014 06:46:31 GMT

←Older revision		Revision as of 06:46, 26 November 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4rt7 is ON HOLD	+	The entry 4rt7 is ON HOLD until Paper Publication

	Authors: Zhang, Y., Zhang, C.		Authors: Zhang, Y., Zhang, C.

	Description: Crystal Structure of FLT3 with a small molecule inhibitor		Description: Crystal Structure of FLT3 with a small molecule inhibitor

OCA: Protected "4rt7" [edit=sysop:move=sysop]

OCA — Wed, 19 Nov 2014 11:34:01 GMT

Protected "4rt7" [edit=sysop:move=sysop]

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Revision as of 11:34, 19 November 2014

OCA: New page: '''Unreleased structure''' The entry 4rt7 is ON HOLD Authors: Zhang, Y., Zhang, C. Description: Crystal Structure of FLT3 with a small molecule inhibitor

OCA — Wed, 19 Nov 2014 11:34:00 GMT

New page: '''Unreleased structure''' The entry 4rt7 is ON HOLD Authors: Zhang, Y., Zhang, C. Description: Crystal Structure of FLT3 with a small molecule inhibitor

New page

'''Unreleased structure'''

The entry 4rt7 is ON HOLD

Authors: Zhang, Y., Zhang, C.

Description: Crystal Structure of FLT3 with a small molecule inhibitor