5v9u - Revision history

OCA at 13:44, 4 October 2023

OCA — Wed, 04 Oct 2023 13:44:29 GMT

←Older revision		Revision as of 13:44, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='5v9u' size='340' side='right'caption='[[5v9u]], [[Resolution\|resolution]] 1.38Å' scene=''>		<StructureSection load='5v9u' size='340' side='right'caption='[[5v9u]], [[Resolution\|resolution]] 1.38Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5v9u]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V9U OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5V9U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5v9u]] 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=5V9U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V9U FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=91S:(S)-1-{4-[6-chloro-8-fluoro-7-(2-fluoro-6-hydroxyphenyl)quinazolin-4-yl]+piperazin-1-yl}propan-1-one'>91S</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <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]] 1.38Å</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=5v9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v9u OCA], [~~http~~://pdbe.org/5v9u PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5v9u RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5v9u PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5v9u ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=91S:(S)-1-{4-[6-chloro-8-fluoro-7-(2-fluoro-6-hydroxyphenyl)quinazolin-4-yl]+piperazin-1-yl}propan-1-one'>91S</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5v9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v9u OCA], [https://pdbe.org/5v9u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v9u RCSB], [https://www.ebi.ac.uk/pdbsum/5v9u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v9u ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Defects in KRAS 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.<ref>PMID:8955068</ref> Defects in KRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[~~http~~://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor. Defects in KRAS are the cause of Noonan syndrome type 3 (NS3) [MIM:[~~http~~://omim.org/entry/609942 609942]]. Noonan syndrome (NS) [MIM:[~~http~~://omim.org/entry/163950 163950]] is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS3 inheritance is autosomal dominant.<ref>PMID:16773572</ref> <ref>PMID:16474405</ref> <ref>PMID:17468812</ref> <ref>PMID:17056636</ref> <ref>PMID:19396835</ref> <ref>PMID:20949621</ref> Defects in KRAS are a cause of gastric cancer (GASC) [MIM:[~~http~~://omim.org/entry/613659 613659]]; also called gastric cancer intestinal or stomach cancer. Gastric cancer is a malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.<ref>PMID:3034404</ref> <ref>PMID:7773929</ref> <ref>PMID:14534542</ref> Note=Defects in KRAS are a cause of pylocytic astrocytoma (PA). Pylocytic astrocytomas are neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors.<ref>PMID:8439212</ref> Defects in KRAS are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[~~http~~://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant. Note=KRAS mutations are involved in cancer development.	+	[https://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN] Defects in KRAS 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.<ref>PMID:8955068</ref> Defects in KRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[https://omim.org/entry/607785 607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor. Defects in KRAS are the cause of Noonan syndrome type 3 (NS3) [MIM:[https://omim.org/entry/609942 609942]. Noonan syndrome (NS) [MIM:[https://omim.org/entry/163950 163950] is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS3 inheritance is autosomal dominant.<ref>PMID:16773572</ref> <ref>PMID:16474405</ref> <ref>PMID:17468812</ref> <ref>PMID:17056636</ref> <ref>PMID:19396835</ref> <ref>PMID:20949621</ref> Defects in KRAS are a cause of gastric cancer (GASC) [MIM:[https://omim.org/entry/613659 613659]; also called gastric cancer intestinal or stomach cancer. Gastric cancer is a malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.<ref>PMID:3034404</ref> <ref>PMID:7773929</ref> <ref>PMID:14534542</ref> Note=Defects in KRAS are a cause of pylocytic astrocytoma (PA). Pylocytic astrocytomas are neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors.<ref>PMID:8439212</ref> Defects in KRAS are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[https://omim.org/entry/115150 115150]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant. Note=KRAS mutations are involved in cancer development.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.	+	[https://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 27:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Babbar, A]]	+	[[Category: Babbar A]]
-	[[Category: Brehmer, D]]	+	[[Category: Brehmer D]]
-	[[Category: Chen~~, J H~~]]	+	[[Category: Chen JH]]
-	[[Category: Chen, Y]]	+	[[Category: Chen Y]]
-	[[Category: Darjania, L]]	+	[[Category: Darjania L]]
-	[[Category: Dashyant, D]]	+	[[Category: Dashyant D]]
-	[[Category: Deng, X]]	+	[[Category: Deng X]]
-	[[Category: Ely, T]]	+	[[Category: Ely T]]
-	[[Category: Feng, J]]	+	[[Category: Feng J]]
-	[[Category: Firdaus~~, S J~~]]	+	[[Category: Firdaus SJ]]
-	[[Category: Guo, X]]	+	[[Category: Guo X]]
-	[[Category: Hansen, R]]	+	[[Category: Hansen R]]
-	[[Category: Hu-Lowe, D]]	+	[[Category: Hu-Lowe D]]
-	[[Category: Janes~~, M R~~]]	+	[[Category: Janes MR]]
-	[[Category: Kessler~~, L V~~]]	+	[[Category: Kessler LV]]
-	[[Category: Kucharski~~, J M~~]]	+	[[Category: Kucharski JM]]
-	[[Category: Li, L S]]	+	[[Category: Li L-S]]
-	[[Category: Li, S]]	+	[[Category: Li S]]
-	[[Category: Liu, Y]]	+	[[Category: Liu Y]]
-	[[Category: Long~~, Y O~~]]	+	[[Category: Long YO]]
-	[[Category: Lorenzi~~, M V~~]]	+	[[Category: Lorenzi MV]]
-	[[Category: Patricelli~~, M P~~]]	+	[[Category: Patricelli MP]]
-	[[Category: Peters, U]]	+	[[Category: Peters U]]
-	[[Category: Ren, P]]	+	[[Category: Ren P]]
-	[[Category: Thach, C]]	+	[[Category: Thach C]]
-	[[Category: Wang, Y]]	+	[[Category: Wang Y]]
-	[[Category: Wu, T]]	+	[[Category: Wu T]]
-	[[Category: Yao, Y]]	+	[[Category: Yao Y]]
-	[[Category: Zarieh, A]]	+	[[Category: Zarieh A]]
-	[[Category: Zarrinkar, P]]	+	[[Category: Zarrinkar P]]
-	[[Category: Zhang, J]]	+	[[Category: Zhang J]]
-	~~[[Category: Covalent inhibitor bound]]~~	+
-	~~[[Category: Gdp bound]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Small gtpase domain]]~~	+
-	~~[[Category: Switch ii pocket~~]]	+

OCA at 08:33, 30 September 2020

OCA — Wed, 30 Sep 2020 08:33:08 GMT

←Older revision		Revision as of 08:33, 30 September 2020
Line 1:		Line 1:

	==Crystal Structure of small molecule ARS-1620 covalently bound to K-Ras G12C==		==Crystal Structure of small molecule ARS-1620 covalently bound to K-Ras G12C==
-	<StructureSection load='5v9u' size='340' side='right' caption='[[5v9u]], [[Resolution\|resolution]] 1.38Å' scene=''>	+	<StructureSection load='5v9u' size='340' side='right'caption='[[5v9u]], [[Resolution\|resolution]] 1.38Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5v9u]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V9U OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5V9U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5v9u]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V9U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5V9U FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=91S:(S)-1-{4-[6-chloro-8-fluoro-7-(2-fluoro-6-hydroxyphenyl)quinazolin-4-yl]+piperazin-1-yl}propan-1-one'>91S</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <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=91S:(S)-1-{4-[6-chloro-8-fluoro-7-(2-fluoro-6-hydroxyphenyl)quinazolin-4-yl]+piperazin-1-yl}propan-1-one'>91S</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=5v9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v9u OCA], [http://pdbe.org/5v9u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v9u RCSB], [http://www.ebi.ac.uk/pdbsum/5v9u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v9u 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=5v9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v9u OCA], [http://pdbe.org/5v9u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v9u RCSB], [http://www.ebi.ac.uk/pdbsum/5v9u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v9u ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5v9u" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5v9u" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[GTPase KRas 3D structures\|GTPase KRas 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Babbar, A]]		[[Category: Babbar, A]]
	[[Category: Brehmer, D]]		[[Category: Brehmer, D]]

OCA at 06:13, 7 February 2018

OCA — Wed, 07 Feb 2018 06:13:34 GMT

←Older revision		Revision as of 06:13, 7 February 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The entry ~~5v9u~~ is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal Structure of small molecule ARS-1620 covalently bound to K-Ras G12C==
		+	<StructureSection load='5v9u' size='340' side='right' caption='[[5v9u]], [[Resolution\|resolution]] 1.38Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5v9u]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V9U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V9U FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=91S:(S)-1-{4-[6-chloro-8-fluoro-7-(2-fluoro-6-hydroxyphenyl)quinazolin-4-yl]+piperazin-1-yl}propan-1-one'>91S</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=5v9u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v9u OCA], [http://pdbe.org/5v9u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v9u RCSB], [http://www.ebi.ac.uk/pdbsum/5v9u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v9u ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Defects in KRAS 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.<ref>PMID:8955068</ref> Defects in KRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[http://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor. Defects in KRAS are the cause of Noonan syndrome type 3 (NS3) [MIM:[http://omim.org/entry/609942 609942]]. Noonan syndrome (NS) [MIM:[http://omim.org/entry/163950 163950]] is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS3 inheritance is autosomal dominant.<ref>PMID:16773572</ref> <ref>PMID:16474405</ref> <ref>PMID:17468812</ref> <ref>PMID:17056636</ref> <ref>PMID:19396835</ref> <ref>PMID:20949621</ref> Defects in KRAS are a cause of gastric cancer (GASC) [MIM:[http://omim.org/entry/613659 613659]]; also called gastric cancer intestinal or stomach cancer. Gastric cancer is a malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.<ref>PMID:3034404</ref> <ref>PMID:7773929</ref> <ref>PMID:14534542</ref> Note=Defects in KRAS are a cause of pylocytic astrocytoma (PA). Pylocytic astrocytomas are neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors.<ref>PMID:8439212</ref> Defects in KRAS are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:[http://omim.org/entry/115150 115150]]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant. Note=KRAS mutations are involved in cancer development.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	KRAS(G12C) was recently identified to be potentially druggable by allele-specific covalent targeting of Cys-12 in vicinity to an inducible allosteric switch II pocket (S-IIP). Success of this approach requires active cycling of KRAS(G12C) between its active-GTP and inactive-GDP conformations as accessibility of the S-IIP is restricted only to the GDP-bound state. This strategy proved feasible for inhibiting mutant KRAS in vitro; however, it is uncertain whether this approach would translate to in vivo. Here, we describe structure-based design and identification of ARS-1620, a covalent compound with high potency and selectivity for KRAS(G12C). ARS-1620 achieves rapid and sustained in vivo target occupancy to induce tumor regression. We use ARS-1620 to dissect oncogenic KRAS dependency and demonstrate that monolayer culture formats significantly underestimate KRAS dependency in vivo. This study provides in vivo evidence that mutant KRAS can be selectively targeted and reveals ARS-1620 as representing a new generation of KRAS(G12C)-specific inhibitors with promising therapeutic potential.

-	~~Authors~~:	+	Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor.,Janes MR, Zhang J, Li LS, Hansen R, Peters U, Guo X, Chen Y, Babbar A, Firdaus SJ, Darjania L, Feng J, Chen JH, Li S, Li S, Long YO, Thach C, Liu Y, Zarieh A, Ely T, Kucharski JM, Kessler LV, Wu T, Yu K, Wang Y, Yao Y, Deng X, Zarrinkar PP, Brehmer D, Dhanak D, Lorenzi MV, Hu-Lowe D, Patricelli MP, Ren P, Liu Y Cell. 2018 Jan 25;172(3):578-589.e17. doi: 10.1016/j.cell.2018.01.006. PMID:29373830<ref>PMID:29373830</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5v9u" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Babbar, A]]
		+	[[Category: Brehmer, D]]
		+	[[Category: Chen, J H]]
		+	[[Category: Chen, Y]]
		+	[[Category: Darjania, L]]
		+	[[Category: Dashyant, D]]
		+	[[Category: Deng, X]]
		+	[[Category: Ely, T]]
		+	[[Category: Feng, J]]
		+	[[Category: Firdaus, S J]]
		+	[[Category: Guo, X]]
		+	[[Category: Hansen, R]]
		+	[[Category: Hu-Lowe, D]]
		+	[[Category: Janes, M R]]
		+	[[Category: Kessler, L V]]
		+	[[Category: Kucharski, J M]]
		+	[[Category: Li, L S]]
		+	[[Category: Li, S]]
		+	[[Category: Liu, Y]]
		+	[[Category: Long, Y O]]
		+	[[Category: Lorenzi, M V]]
		+	[[Category: Patricelli, M P]]
		+	[[Category: Peters, U]]
		+	[[Category: Ren, P]]
		+	[[Category: Thach, C]]
		+	[[Category: Wang, Y]]
		+	[[Category: Wu, T]]
		+	[[Category: Yao, Y]]
		+	[[Category: Zarieh, A]]
		+	[[Category: Zarrinkar, P]]
		+	[[Category: Zhang, J]]
		+	[[Category: Covalent inhibitor bound]]
		+	[[Category: Gdp bound]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Small gtpase domain]]
		+	[[Category: Switch ii pocket]]

OCA at 11:13, 19 April 2017

OCA — Wed, 19 Apr 2017 11:13:10 GMT

←Older revision		Revision as of 11:13, 19 April 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5v9u is ON HOLD	+	The entry 5v9u is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "5v9u" [edit=sysop:move=sysop]

OCA — Wed, 05 Apr 2017 11:50:22 GMT

Protected "5v9u" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:50, 5 April 2017

OCA: New page: '''Unreleased structure''' The entry 5v9u is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 05 Apr 2017 11:50:21 GMT

New page: '''Unreleased structure''' The entry 5v9u is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5v9u is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]