5oco - Revision history

OCA at 09:40, 6 December 2023

2023-12-06T09:40:14Z

← Older revision		Revision as of 09:40, 6 December 2023
Line 3:		Line 3:
	<StructureSection load='5oco' size='340' side='right'caption='[[5oco]], [[Resolution\|resolution]] 1.66Å' scene=''>		<StructureSection load='5oco' size='340' side='right'caption='[[5oco]], [[Resolution\|resolution]] 1.66Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5oco]] is a 6 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=5OCO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5OCO FirstGlance]. <br>		<table><tr><td colspan='2'>[[5oco]] is a 6 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=5OCO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OCO FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9RK:~{N}-[[(3~{R})-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]furan-2-carboxamide'>9RK</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 1.66Å</td></tr>
	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr>~~		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9RK:~{N}-[[(3~{R})-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]furan-2-carboxamide'>9RK</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5oco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oco OCA], [https://pdbe.org/5oco PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oco RCSB], [https://www.ebi.ac.uk/pdbsum/5oco PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oco ProSAT]</span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5oco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oco OCA], [~~http~~://pdbe.org/5oco PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5oco RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5oco PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5oco 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 29:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Cruz-Migoni, A]]		[[Category: Cruz-Migoni A]]
	[[Category: Ehebauer~~, M T~~]]		[[Category: Ehebauer MT]]
	[[Category: Phillips~~, S E.V~~]]		[[Category: Phillips SEV]]
	[[Category: Quevedo~~, C E~~]]		[[Category: Quevedo CE]]
	[[Category: Rabbitts~~, T H]]~~		[[Category: Rabbitts TH]]
	~~[[Category: Domain antibody]]~~
	~~[[Category: Drug fragment screening]]~~
	~~[[Category: Hydrolase]]~~
	~~[[Category: Small molecule~~]]

OCA at 06:54, 16 October 2019

2019-10-16T06:54:13Z

← Older revision		Revision as of 06:54, 16 October 2019
Line 1:		Line 1:

	==Discovery of small molecules binding to KRAS via high affinity antibody fragment competition method.==		==Discovery of small molecules binding to KRAS via high affinity antibody fragment competition method.==
	<StructureSection load='5oco' size='340' side='right' caption='[[5oco]], [[Resolution\|resolution]] 1.66Å' scene=''>		<StructureSection load='5oco' size='340' side='right'caption='[[5oco]], [[Resolution\|resolution]] 1.66Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5oco]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OCO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OCO FirstGlance]. <br>		<table><tr><td colspan='2'>[[5oco]] is a 6 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=5OCO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OCO FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9RK:~{N}-[[(3~{R})-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]furan-2-carboxamide'>9RK</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9RK:~{N}-[[(3~{R})-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]furan-2-carboxamide'>9RK</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></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='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=5oco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oco OCA], [http://pdbe.org/5oco PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oco RCSB], [http://www.ebi.ac.uk/pdbsum/5oco PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oco ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5oco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oco OCA], [http://pdbe.org/5oco PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oco RCSB], [http://www.ebi.ac.uk/pdbsum/5oco PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oco ProSAT]</span></td></tr>
	</table>		</table>
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5oco" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5oco" 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: Large Structures]]
	[[Category: Cruz-Migoni, A]]		[[Category: Cruz-Migoni, A]]
	[[Category: Ehebauer, M T]]		[[Category: Ehebauer, M T]]

OCA at 05:58, 22 August 2018

2018-08-22T05:58:50Z

← Older revision		Revision as of 05:58, 22 August 2018
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	The entry ~~5oco~~ is ~~ON HOLD~~ ~~until Oct 03 2019~~		==Discovery of small molecules binding to KRAS via high affinity antibody fragment competition method.==
			<StructureSection load='5oco' size='340' side='right' caption='[[5oco]], [[Resolution\|resolution]] 1.66Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[5oco]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OCO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OCO FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9RK:~{N}-[[(3~{R})-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]furan-2-carboxamide'>9RK</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
			<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</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=5oco FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oco OCA], [http://pdbe.org/5oco PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oco RCSB], [http://www.ebi.ac.uk/pdbsum/5oco PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oco 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 ==
			Targeting specific protein-protein interactions (PPIs) is an attractive concept for drug development, but hard to implement since intracellular antibodies do not penetrate cells and most small-molecule drugs are considered unsuitable for PPI inhibition. A potential solution to these problems is to select intracellular antibody fragments to block PPIs, use these antibody fragments for target validation in disease models and finally derive small molecules overlapping the antibody-binding site. Here, we explore this strategy using an anti-mutant RAS antibody fragment as a competitor in a small-molecule library screen for identifying RAS-binding compounds. The initial hits are optimized by structure-based design, resulting in potent RAS-binding compounds that interact with RAS inside the cells, prevent RAS-effector interactions and inhibit endogenous RAS-dependent signalling. Our results may aid RAS-dependent cancer drug development and demonstrate a general concept for developing small compounds to replace intracellular antibody fragments, enabling rational drug development to target validated PPIs.

	~~Authors:~~ Cruz-Migoni, A., Ehebauer, ~~M.T.~~, ~~Phillips~~, ~~S.E.V.~~, ~~Quevedo~~, C.E.~~, Rabbitts, T~~.H.		Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment.,Quevedo CE, Cruz-Migoni A, Bery N, Miller A, Tanaka T, Petch D, Bataille CJR, Lee LYW, Fallon PS, Tulmin H, Ehebauer MT, Fernandez-Fuentes N, Russell AJ, Carr SB, Phillips SEV, Rabbitts TH Nat Commun. 2018 Aug 9;9(1):3169. doi: 10.1038/s41467-018-05707-2. PMID:30093669<ref>PMID:30093669</ref>

	~~Description: Discovery~~ of ~~small molecules binding to KRAS via high affinity antibody fragment competition method~~.		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[Category~~: ~~Unreleased Structures]]~~		</div>
	~~[[Category: Rabbitts, T.H]]~~		<div class="pdbe-citations 5oco" style="background-color:#fffaf0;"></div>
	~~[[Category: Quevedo, C.E]]~~		== References ==
	~~[[Category: Phillips, S.E.V]]~~		<references/>
	~~[[Category: Ehebauer, M.T]]~~		__TOC__
			</StructureSection>
	[[Category: Cruz-Migoni, A]]		[[Category: Cruz-Migoni, A]]
			[[Category: Ehebauer, M T]]
			[[Category: Phillips, S E.V]]
			[[Category: Quevedo, C E]]
			[[Category: Rabbitts, T H]]
			[[Category: Domain antibody]]
			[[Category: Drug fragment screening]]
			[[Category: Hydrolase]]
			[[Category: Small molecule]]

OCA at 04:41, 9 May 2018

2018-05-09T04:41:59Z

← Older revision		Revision as of 04:41, 9 May 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 5oco is ON HOLD		The entry 5oco is ON HOLD until Oct 03 2019

	Authors: Cruz-Migoni, A., Ehebauer, M.T., Phillips, S.E.V., Quevedo, C.E., Rabbitts, T.H.		Authors: Cruz-Migoni, A., Ehebauer, M.T., Phillips, S.E.V., Quevedo, C.E., Rabbitts, T.H.
Line 7:		Line 7:
	Description: Discovery of small molecules binding to KRAS via high affinity antibody fragment competition method.		Description: Discovery of small molecules binding to KRAS via high affinity antibody fragment competition method.
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
			[[Category: Rabbitts, T.H]]
			[[Category: Quevedo, C.E]]
			[[Category: Phillips, S.E.V]]
	[[Category: Ehebauer, M.T]]		[[Category: Ehebauer, M.T]]
	~~[[Category: Phillips, S.E.V]]~~
	[[Category: Cruz-Migoni, A]]		[[Category: Cruz-Migoni, A]]
	~~[[Category: Rabbitts, T.H]]~~
	~~[[Category: Quevedo, C.E]]~~

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

2017-09-27T12:16:52Z

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

← Older revision	Revision as of 12:16, 27 September 2017
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5oco is ON HOLD Authors: Cruz-Migoni, A., Ehebauer, M.T., Phillips, S.E.V., Quevedo, C.E., Rabbitts, T.H. Description: Discovery of small molecules...

2017-09-27T12:16:51Z

New page: '''Unreleased structure''' The entry 5oco is ON HOLD Authors: Cruz-Migoni, A., Ehebauer, M.T., Phillips, S.E.V., Quevedo, C.E., Rabbitts, T.H. Description: Discovery of small molecules...

New page

'''Unreleased structure'''

The entry 5oco is ON HOLD

Authors: Cruz-Migoni, A., Ehebauer, M.T., Phillips, S.E.V., Quevedo, C.E., Rabbitts, T.H.

Description: Discovery of small molecules binding to KRAS via high affinity antibody fragment competition method.
[[Category: Unreleased Structures]]
[[Category: Ehebauer, M.T]]
[[Category: Phillips, S.E.V]]
[[Category: Cruz-Migoni, A]]
[[Category: Rabbitts, T.H]]
[[Category: Quevedo, C.E]]