4m1y - Revision history

OCA at 16:30, 20 September 2023

2023-09-20T16:30:47Z

←Older revision		Revision as of 16:30, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4m1y]] is a 3 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=4M1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M1Y FirstGlance]. <br>		<table><tr><td colspan='2'>[[4m1y]] is a 3 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=4M1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M1Y FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=21S:N-{1-[N-(5,7-DICHLORO-2,1,3-BENZOTHIADIAZOL-4-YL)GLYCYL]PIPERIDIN-4-YL}ETHANESULFONAMIDE'>21S</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</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]] 1.491Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=21S:N-{1-[N-(5,7-DICHLORO-2,1,3-BENZOTHIADIAZOL-4-YL)GLYCYL]PIPERIDIN-4-YL}ETHANESULFONAMIDE'>21S</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</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=4m1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m1y OCA], [https://pdbe.org/4m1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m1y RCSB], [https://www.ebi.ac.uk/pdbsum/4m1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m1y 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=4m1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m1y OCA], [https://pdbe.org/4m1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m1y RCSB], [https://www.ebi.ac.uk/pdbsum/4m1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m1y ProSAT]</span></td></tr>
	</table>		</table>

OCA at 10:48, 21 December 2022

2022-12-21T10:48:05Z

←Older revision		Revision as of 10:48, 21 December 2022
Line 1:		Line 1:

	==Crystal Structure of small molecule vinylsulfonamide 15 covalently bound to K-Ras G12C==		==Crystal Structure of small molecule vinylsulfonamide 15 covalently bound to K-Ras G12C==
-	<StructureSection load='4m1y' size='340' side='right' caption='[[4m1y]], [[Resolution\|resolution]] 1.49Å' scene=''>	+	<StructureSection load='4m1y' size='340' side='right'caption='[[4m1y]], [[Resolution\|resolution]] 1.49Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4m1y]] is a 3 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=4M1Y OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4M1Y FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4m1y]] is a 3 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=4M1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M1Y FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=21S:N-{1-[N-(5,7-DICHLORO-2,1,3-BENZOTHIADIAZOL-4-YL)GLYCYL]PIPERIDIN-4-YL}ETHANESULFONAMIDE'>21S</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=21S:N-{1-[N-(5,7-DICHLORO-2,1,3-BENZOTHIADIAZOL-4-YL)GLYCYL]PIPERIDIN-4-YL}ETHANESULFONAMIDE'>21S</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4l8g\|4l8g]], [[4luc\|4luc]], [[4lyf\|4lyf]], [[4lyj\|4lyj]], [[4m1o\|4m1o]], [[4l9w\|4l9w]], [[4l9s\|4l9s]], [[4lpk\|4lpk]], [[4lv6\|4lv6]], [[4m1s\|4m1s]], [[4m1t\|4m1t]], [[4m1w\|4m1w]], [[4lyh\|4lyh]], [[4lrw\|4lrw]], [[4m21\|4m21]], [[4m22\|4m22]]</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=4m1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m1y OCA], [https://pdbe.org/4m1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m1y RCSB], [https://www.ebi.ac.uk/pdbsum/4m1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m1y ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KRAS, KRAS isoform 2B, KRAS2, RASK2 ([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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4m1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m1y OCA], [~~http~~://pdbe.org/4m1y PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4m1y RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4m1y PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4m1y 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 22:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4m1y" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4m1y" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[GTPase KRas 3D structures\|GTPase KRas 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Ostrem, J M~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Peters, U~~]]	+	[[Category: Ostrem JM]]
-	[[Category: ~~Shokat, K M~~]]	+	[[Category: Peters U]]
-	[[Category: ~~Sos, M L~~]]	+	[[Category: Shokat KM]]
-	[[Category: ~~Wells, J A~~]]	+	[[Category: Sos ML]]
-	[[Category: ~~Covalent binder]]~~	+	[[Category: Wells JA]]
-	~~[[Category: Gdp bound]]~~	+
-	~~[[Category: Gtpase]]~~	+
-	~~[[Category: Signaling protein-inhibitor complex]]~~	+
-	~~[[Category: Small molecule inhibitor~~]]	+

OCA at 18:48, 11 August 2016

2016-08-11T18:48:11Z

←Older revision		Revision as of 18:48, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal Structure of small molecule vinylsulfonamide 15 covalently bound to K-Ras G12C==		==Crystal Structure of small molecule vinylsulfonamide 15 covalently bound to K-Ras G12C==
	<StructureSection load='4m1y' size='340' side='right' caption='[[4m1y]], [[Resolution\|resolution]] 1.49Å' scene=''>		<StructureSection load='4m1y' size='340' side='right' caption='[[4m1y]], [[Resolution\|resolution]] 1.49Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4l8g\|4l8g]], [[4luc\|4luc]], [[4lyf\|4lyf]], [[4lyj\|4lyj]], [[4m1o\|4m1o]], [[4l9w\|4l9w]], [[4l9s\|4l9s]], [[4lpk\|4lpk]], [[4lv6\|4lv6]], [[4m1s\|4m1s]], [[4m1t\|4m1t]], [[4m1w\|4m1w]], [[4lyh\|4lyh]], [[4lrw\|4lrw]], [[4m21\|4m21]], [[4m22\|4m22]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4l8g\|4l8g]], [[4luc\|4luc]], [[4lyf\|4lyf]], [[4lyj\|4lyj]], [[4m1o\|4m1o]], [[4l9w\|4l9w]], [[4l9s\|4l9s]], [[4lpk\|4lpk]], [[4lv6\|4lv6]], [[4m1s\|4m1s]], [[4m1t\|4m1t]], [[4m1w\|4m1w]], [[4lyh\|4lyh]], [[4lrw\|4lrw]], [[4m21\|4m21]], [[4m22\|4m22]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KRAS, KRAS isoform 2B, KRAS2, RASK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KRAS, KRAS isoform 2B, KRAS2, RASK2 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4m1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m1y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m1y RCSB], [http://www.ebi.ac.uk/pdbsum/4m1y 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=4m1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m1y OCA], [http://pdbe.org/4m1y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m1y RCSB], [http://www.ebi.ac.uk/pdbsum/4m1y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m1y ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	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 4m1y" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:18, 5 January 2015

2015-01-05T09:18:10Z

←Older revision		Revision as of 09:18, 5 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4m1y\| PDB=4m1y \| SCENE= }}~~	+	==Crystal Structure of small molecule vinylsulfonamide 15 covalently bound to K-Ras G12C==
-	===Crystal Structure of small molecule vinylsulfonamide 15 covalently bound to K-Ras G12C===	+	<StructureSection load='4m1y' size='340' side='right' caption='[[4m1y]], [[Resolution\|resolution]] 1.49Å' scene=''>
-	{~~{ABSTRACT_PUBMED_24256730}~~}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4m1y]] is a 3 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=4M1Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M1Y FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=21S:N-{1-[N-(5,7-DICHLORO-2,1,3-BENZOTHIADIAZOL-4-YL)GLYCYL]PIPERIDIN-4-YL}ETHANESULFONAMIDE'>21S</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4l8g\|4l8g]], [[4luc\|4luc]], [[4lyf\|4lyf]], [[4lyj\|4lyj]], [[4m1o\|4m1o]], [[4l9w\|4l9w]], [[4l9s\|4l9s]], [[4lpk\|4lpk]], [[4lv6\|4lv6]], [[4m1s\|4m1s]], [[4m1t\|4m1t]], [[4m1w\|4m1w]], [[4lyh\|4lyh]], [[4lrw\|4lrw]], [[4m21\|4m21]], [[4m22\|4m22]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KRAS, KRAS isoform 2B, KRAS2, RASK2 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4m1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m1y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4m1y RCSB], [http://www.ebi.ac.uk/pdbsum/4m1y PDBsum]</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.		[[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 ==
-	==Function==	+
	[[http://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.		[[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 ==
		+	Somatic mutations in the small GTPase K-Ras are the most common activating lesions found in human cancer, and are generally associated with poor response to standard therapies. Efforts to target this oncogene directly have faced difficulties owing to its picomolar affinity for GTP/GDP and the absence of known allosteric regulatory sites. Oncogenic mutations result in functional activation of Ras family proteins by impairing GTP hydrolysis. With diminished regulation by GTPase activity, the nucleotide state of Ras becomes more dependent on relative nucleotide affinity and concentration. This gives GTP an advantage over GDP and increases the proportion of active GTP-bound Ras. Here we report the development of small molecules that irreversibly bind to a common oncogenic mutant, K-Ras(G12C). These compounds rely on the mutant cysteine for binding and therefore do not affect the wild-type protein. Crystallographic studies reveal the formation of a new pocket that is not apparent in previous structures of Ras, beneath the effector binding switch-II region. Binding of these inhibitors to K-Ras(G12C) disrupts both switch-I and switch-II, subverting the native nucleotide preference to favour GDP over GTP and impairing binding to Raf. Our data provide structure-based validation of a new allosteric regulatory site on Ras that is targetable in a mutant-specific manner.

-	~~==About this Structure==~~	+	K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions.,Ostrem JM, Peters U, Sos ML, Wells JA, Shokat KM Nature. 2013 Nov 28;503(7477):548-51. doi: 10.1038/nature12796. Epub 2013 Nov 20. PMID:24256730<ref>PMID:24256730</ref>
-	~~[[4m1y]] is a 3 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=4M1Y OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:024256730</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Ostrem, J M.]]	+	[[Category: Ostrem, J M]]
-	[[Category: Peters, U.]]	+	[[Category: Peters, U]]
-	[[Category: Shokat, K M.]]	+	[[Category: Shokat, K M]]
-	[[Category: Sos, M L.]]	+	[[Category: Sos, M L]]
-	[[Category: Wells, J A.]]	+	[[Category: Wells, J A]]
	[[Category: Covalent binder]]		[[Category: Covalent binder]]
	[[Category: Gdp bound]]		[[Category: Gdp bound]]

OCA at 07:58, 18 December 2013

2013-12-18T07:58:43Z

←Older revision		Revision as of 07:58, 18 December 2013
Line 1:		Line 1:
	{{STRUCTURE_4m1y\| PDB=4m1y \| SCENE= }}		{{STRUCTURE_4m1y\| PDB=4m1y \| SCENE= }}
	===Crystal Structure of small molecule vinylsulfonamide 15 covalently bound to K-Ras G12C===		===Crystal Structure of small molecule vinylsulfonamide 15 covalently bound to K-Ras G12C===
		+	{{ABSTRACT_PUBMED_24256730}}

	==Disease==		==Disease==
Line 9:		Line 10:

	==About this Structure==		==About this Structure==
-	[[4m1y]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M1Y OCA].	+	[[4m1y]] is a 3 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=4M1Y OCA].

	==Reference==		==Reference==
-	<references group="xtra"/><references/>	+	<ref group="xtra">PMID:024256730</ref><references group="xtra"/><references/>
		+	[[Category: Human]]
	[[Category: Ostrem, J M.]]		[[Category: Ostrem, J M.]]
	[[Category: Peters, U.]]		[[Category: Peters, U.]]

OCA at 10:34, 27 November 2013

2013-11-27T10:34:10Z

←Older revision		Revision as of 10:34, 27 November 2013
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4m1y\| PDB=4m1y \| SCENE= }}
		+	===Crystal Structure of small molecule vinylsulfonamide 15 covalently bound to K-Ras G12C===

-	The entry ~~4m1y~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==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.

-	~~Authors~~: ~~Ostrem, J~~.M.~~, Peters, U., Sos, M.L., Wells, J.A., Shokat, K.M~~.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/RASK_HUMAN RASK_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.

-	~~Description: Crystal~~ Structure ~~of small molecule vinylsulfonamide 15 covalently bound to~~ K-~~Ras G12C~~	+	==About this Structure==
		+	[[4m1y]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M1Y OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Ostrem, J M.]]
		+	[[Category: Peters, U.]]
		+	[[Category: Shokat, K M.]]
		+	[[Category: Sos, M L.]]
		+	[[Category: Wells, J A.]]
		+	[[Category: Covalent binder]]
		+	[[Category: Gdp bound]]
		+	[[Category: Gtpase]]
		+	[[Category: Signaling protein-inhibitor complex]]
		+	[[Category: Small molecule inhibitor]]

OCA at 06:51, 28 August 2013

2013-08-28T06:51:15Z

←Older revision		Revision as of 06:51, 28 August 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4m1y is ON HOLD	+	The entry 4m1y is ON HOLD until Paper Publication

	Authors: Ostrem, J.M., Peters, U., Sos, M.L., Wells, J.A., Shokat, K.M.		Authors: Ostrem, J.M., Peters, U., Sos, M.L., Wells, J.A., Shokat, K.M.

	Description: Crystal Structure of small molecule vinylsulfonamide 15 covalently bound to K-Ras G12C		Description: Crystal Structure of small molecule vinylsulfonamide 15 covalently bound to K-Ras G12C

OCA: Protected "4m1y" [edit=sysop:move=sysop]

2013-08-14T07:22:39Z

Protected "4m1y" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:22, 14 August 2013

OCA: New page: '''Unreleased structure''' The entry 4m1y is ON HOLD Authors: Ostrem, J.M., Peters, U., Sos, M.L., Wells, J.A., Shokat, K.M. Description: Crystal Structure of small molecule vinylsulfo...

2013-08-14T07:22:39Z

New page: '''Unreleased structure''' The entry 4m1y is ON HOLD Authors: Ostrem, J.M., Peters, U., Sos, M.L., Wells, J.A., Shokat, K.M. Description: Crystal Structure of small molecule vinylsulfo...

New page

'''Unreleased structure'''

The entry 4m1y is ON HOLD

Authors: Ostrem, J.M., Peters, U., Sos, M.L., Wells, J.A., Shokat, K.M.

Description: Crystal Structure of small molecule vinylsulfonamide 15 covalently bound to K-Ras G12C