4epx - Revision history

OCA at 15:06, 14 March 2024

OCA — Thu, 14 Mar 2024 15:06:57 GMT

←Older revision		Revision as of 15:06, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4epx]] 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=4EPX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EPX FirstGlance]. <br>		<table><tr><td colspan='2'>[[4epx]] 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=4EPX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EPX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0QR:N-(6-AMINOPYRIDIN-2-YL)-4-FLUOROBENZENESULFONAMIDE'>0QR</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.76Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0QR:N-(6-AMINOPYRIDIN-2-YL)-4-FLUOROBENZENESULFONAMIDE'>0QR</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4epx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4epx OCA], [https://pdbe.org/4epx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4epx RCSB], [https://www.ebi.ac.uk/pdbsum/4epx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4epx 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=4epx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4epx OCA], [https://pdbe.org/4epx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4epx RCSB], [https://www.ebi.ac.uk/pdbsum/4epx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4epx ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[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.	+	[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 ==
-	[[https://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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Looking for fragments: A fragment-based screen using NMR spectroscopy was applied to discover ligands that bind to the GTPase K-Ras and modulate the activity of the nucleotide exchange factor Sos. Structural data on how these fragment-derived hits bind to the guanosine diphosphate-K-Ras complex provides a starting point for the future discovery of drugs that target K-Ras activation and signaling.	+
-		+
-	Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation.,Sun Q, Burke JP, Phan J, Burns MC, Olejniczak ET, Waterson AG, Lee T, Rossanese OW, Fesik SW Angew Chem Int Ed Engl. 2012 May 8. doi: 10.1002/anie.201201358. PMID:22566140<ref>PMID:22566140</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4epx" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==

OCA at 07:22, 28 September 2022

OCA — Wed, 28 Sep 2022 07:22:43 GMT

←Older revision		Revision as of 07:22, 28 September 2022
Line 1:		Line 1:

	==Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-mediated Activation==		==Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-mediated Activation==
-	<StructureSection load='4epx' size='340' side='right' caption='[[4epx]], [[Resolution\|resolution]] 1.76Å' scene=''>	+	<StructureSection load='4epx' size='340' side='right'caption='[[4epx]], [[Resolution\|resolution]] 1.76Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4epx]] 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=4EPX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4EPX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4epx]] 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=4EPX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EPX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0QR:N-(6-AMINOPYRIDIN-2-YL)-4-FLUOROBENZENESULFONAMIDE'>0QR</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0QR:N-(6-AMINOPYRIDIN-2-YL)-4-FLUOROBENZENESULFONAMIDE'>0QR</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4epr\|4epr]], [[4ept\|4ept]], [[4epv\|4epv]], [[4epy\|4epy]]</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=4epx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4epx OCA], [https://pdbe.org/4epx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4epx RCSB], [https://www.ebi.ac.uk/pdbsum/4epx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4epx ProSAT]</span></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KRAS, KRAS2, RASK2 ([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/Small_monomeric_GTPase Small monomeric GTPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.5.2 3.6.5.2] </span></td></tr>	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4epx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4epx OCA], [~~http~~://pdbe.org/4epx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4epx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4epx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4epx 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 23:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4epx" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4epx" 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: ~~Small monomeric GTPase~~]]	+	[[Category: Large Structures]]
-	[[Category: Burke~~, J P~~]]	+	[[Category: Burke JP]]
-	[[Category: Burns~~, M C~~]]	+	[[Category: Burns MC]]
-	[[Category: Fesik~~, S W~~]]	+	[[Category: Fesik SW]]
-	[[Category: Lee, T]]	+	[[Category: Lee T]]
-	[[Category: Olejniczak~~, E T~~]]	+	[[Category: Olejniczak ET]]
-	[[Category: Phan, J]]	+	[[Category: Phan J]]
-	[[Category: Rossanese~~, O W~~]]	+	[[Category: Rossanese OW]]
-	[[Category: Sun, Q]]	+	[[Category: Sun Q]]
-	[[Category: Waterson~~, A G]]~~	+	[[Category: Waterson AG]]
-	~~[[Category: Binder]]~~	+
-	~~[[Category: Cytosol]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Inhibitor of sos-mediated activation]]~~	+
-	~~[[Category: Pi3k]]~~	+
-	~~[[Category: Raf]]~~	+
-	~~[[Category: Ral]]~~	+
-	~~[[Category: Signaling transduction]]~~	+
-	~~[[Category: Small gtpase]]~~	+
-	~~[[Category: So~~]]	+

OCA at 15:25, 11 August 2016

OCA — Thu, 11 Aug 2016 15:25:16 GMT

←Older revision		Revision as of 15:25, 11 August 2016
Line 1:		Line 1:
		+
	==Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-mediated Activation==		==Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-mediated Activation==
	<StructureSection load='4epx' size='340' side='right' caption='[[4epx]], [[Resolution\|resolution]] 1.76Å' scene=''>		<StructureSection load='4epx' size='340' side='right' caption='[[4epx]], [[Resolution\|resolution]] 1.76Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4epx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EPX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EPX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4epx]] 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=4EPX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EPX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0QR:N-(6-AMINOPYRIDIN-2-YL)-4-FLUOROBENZENESULFONAMIDE'>0QR</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0QR:N-(6-AMINOPYRIDIN-2-YL)-4-FLUOROBENZENESULFONAMIDE'>0QR</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4epr\|4epr]], [[4ept\|4ept]], [[4epv\|4epv]], [[4epy\|4epy]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4epr\|4epr]], [[4ept\|4ept]], [[4epv\|4epv]], [[4epy\|4epy]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KRAS, KRAS2, RASK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KRAS, KRAS2, RASK2 ([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/Small_monomeric_GTPase Small monomeric GTPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.5.2 3.6.5.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Small_monomeric_GTPase Small monomeric GTPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.5.2 3.6.5.2] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4epx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4epx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4epx RCSB], [http://www.ebi.ac.uk/pdbsum/4epx 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=4epx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4epx OCA], [http://pdbe.org/4epx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4epx RCSB], [http://www.ebi.ac.uk/pdbsum/4epx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4epx ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	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 4epx" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Small monomeric GTPase]]		[[Category: Small monomeric GTPase]]
	[[Category: Burke, J P]]		[[Category: Burke, J P]]

OCA at 09:49, 25 January 2015

OCA — Sun, 25 Jan 2015 09:49:05 GMT

←Older revision		Revision as of 09:49, 25 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4epx\| PDB=4epx \| SCENE= }}~~	+	==Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-mediated Activation==
-	===Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-mediated Activation===	+	<StructureSection load='4epx' size='340' side='right' caption='[[4epx]], [[Resolution\|resolution]] 1.76Å' scene=''>
-	~~{{ABSTRACT_PUBMED_22566140}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4epx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EPX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EPX FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0QR:N-(6-AMINOPYRIDIN-2-YL)-4-FLUOROBENZENESULFONAMIDE'>0QR</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	[[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.	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4epr\|4epr]], [[4ept\|4ept]], [[4epv\|4epv]], [[4epy\|4epy]]</td></tr>
-		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KRAS, KRAS2, RASK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-	==Function==	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Small_monomeric_GTPase Small monomeric GTPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.5.2 3.6.5.2] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4epx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4epx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4epx RCSB], [http://www.ebi.ac.uk/pdbsum/4epx 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.
		+	== 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 ==
		+	Looking for fragments: A fragment-based screen using NMR spectroscopy was applied to discover ligands that bind to the GTPase K-Ras and modulate the activity of the nucleotide exchange factor Sos. Structural data on how these fragment-derived hits bind to the guanosine diphosphate-K-Ras complex provides a starting point for the future discovery of drugs that target K-Ras activation and signaling.

-	~~==About this Structure==~~	+	Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation.,Sun Q, Burke JP, Phan J, Burns MC, Olejniczak ET, Waterson AG, Lee T, Rossanese OW, Fesik SW Angew Chem Int Ed Engl. 2012 May 8. doi: 10.1002/anie.201201358. PMID:22566140<ref>PMID:22566140</ref>
-	~~[[4epx]] is a 1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http~~:/~~/oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=4EPX OCA].~~	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:022566140</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Small monomeric GTPase]]		[[Category: Small monomeric GTPase]]
-	[[Category: Burke, J P.]]	+	[[Category: Burke, J P]]
-	[[Category: Burns, M C.]]	+	[[Category: Burns, M C]]
-	[[Category: Fesik, S W.]]	+	[[Category: Fesik, S W]]
-	[[Category: Lee, T.]]	+	[[Category: Lee, T]]
-	[[Category: Olejniczak, E T.]]	+	[[Category: Olejniczak, E T]]
-	[[Category: Phan, J.]]	+	[[Category: Phan, J]]
-	[[Category: Rossanese, O W.]]	+	[[Category: Rossanese, O W]]
-	[[Category: Sun, Q.]]	+	[[Category: Sun, Q]]
-	[[Category: Waterson, A G.]]	+	[[Category: Waterson, A G]]
	[[Category: Binder]]		[[Category: Binder]]
	[[Category: Cytosol]]		[[Category: Cytosol]]

OCA at 00:19, 25 March 2013

OCA — Mon, 25 Mar 2013 00:19:15 GMT

←Older revision		Revision as of 00:19, 25 March 2013
Line 1:		Line 1:
-	[[Image:4epx.png\|left\|200px]]
-
	{{STRUCTURE_4epx\| PDB=4epx \| SCENE= }}		{{STRUCTURE_4epx\| PDB=4epx \| SCENE= }}
-
	===Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-mediated Activation===		===Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-mediated Activation===
		+	{{ABSTRACT_PUBMED_22566140}}

-	~~{{ABSTRACT_PUBMED_22566140}}~~	+	==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.

	==About this Structure==		==About this Structure==
Line 11:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:022566140</ref><references group="xtra"/>	+	<ref group="xtra">PMID:022566140</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Small monomeric GTPase]]		[[Category: Small monomeric GTPase]]

OCA at 06:29, 25 July 2012

OCA — Wed, 25 Jul 2012 06:29:05 GMT

←Older revision		Revision as of 06:29, 25 July 2012
Line 1:		Line 1:
-	[[Image:4epx.~~jpg~~\|left\|200px]]	+	[[Image:4epx.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_4epx", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_4epx\| PDB=4epx \| SCENE= }}		{{STRUCTURE_4epx\| PDB=4epx \| SCENE= }}

	===Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-mediated Activation===		===Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-mediated Activation===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_22566140}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 22566140 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_22566140}}		{{ABSTRACT_PUBMED_22566140}}

OCA at 06:06, 23 May 2012

OCA — Wed, 23 May 2012 06:06:36 GMT

←Older revision		Revision as of 06:06, 23 May 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4epx.jpg\|left\|200px]]

-	The ~~entry 4epx~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_4epx", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_4epx\| PDB=4epx \| SCENE= }}

-	~~Authors: Sun, Q., Burke, J.P., Phan, J., Burns, M.C., Olejniczak, E.T., Waterson, A.G., Lee, T., Rossanese, O.W., Fesik, S.W.~~	+	===Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-mediated Activation===

-	~~Description: Discovery of Small Molecules that Bind~~ to K-~~Ras and Inhibit Sos~~-mediated ~~Activation~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22566140}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22566140 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22566140}}
		+
		+	==About this Structure==
		+	[[4epx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EPX OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022566140</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Small monomeric GTPase]]
		+	[[Category: Burke, J P.]]
		+	[[Category: Burns, M C.]]
		+	[[Category: Fesik, S W.]]
		+	[[Category: Lee, T.]]
		+	[[Category: Olejniczak, E T.]]
		+	[[Category: Phan, J.]]
		+	[[Category: Rossanese, O W.]]
		+	[[Category: Sun, Q.]]
		+	[[Category: Waterson, A G.]]
		+	[[Category: Binder]]
		+	[[Category: Cytosol]]
		+	[[Category: Hydrolase]]
		+	[[Category: Inhibitor of sos-mediated activation]]
		+	[[Category: Pi3k]]
		+	[[Category: Raf]]
		+	[[Category: Ral]]
		+	[[Category: Signaling transduction]]
		+	[[Category: Small gtpase]]
		+	[[Category: So]]

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

OCA — Wed, 25 Apr 2012 08:56:50 GMT

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

←Older revision

Revision as of 08:56, 25 April 2012

OCA: New page: '''Unreleased structure''' The entry 4epx is ON HOLD until Paper Publication Authors: Sun, Q., Burke, J.P., Phan, J., Burns, M.C., Olejniczak, E.T., Waterson, A.G., Lee, T., Rossanese, ...

OCA — Wed, 25 Apr 2012 08:56:49 GMT

New page: '''Unreleased structure''' The entry 4epx is ON HOLD until Paper Publication Authors: Sun, Q., Burke, J.P., Phan, J., Burns, M.C., Olejniczak, E.T., Waterson, A.G., Lee, T., Rossanese, ...

New page

'''Unreleased structure'''

The entry 4epx is ON HOLD until Paper Publication

Authors: Sun, Q., Burke, J.P., Phan, J., Burns, M.C., Olejniczak, E.T., Waterson, A.G., Lee, T., Rossanese, O.W., Fesik, S.W.

Description: Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-mediated Activation