6bvm - Revision history

OCA at 14:51, 4 October 2023

2023-10-04T14:51:13Z

←Older revision		Revision as of 14:51, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='6bvm' size='340' side='right'caption='[[6bvm]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='6bvm' size='340' side='right'caption='[[6bvm]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6bvm]] 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=6BVM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6BVM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6bvm]] 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=6BVM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BVM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EBV:(2S)-2-amino-1-[(3aR,6aS)-5-[(5-chloro-1H-indol-3-yl)methyl]hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]-3-(1H-indol-3-yl)propan-1-one'>EBV</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.796Å</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=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=EBV:(2S)-2-amino-1-[(3aR,6aS)-5-[(5-chloro-1H-indol-3-yl)methyl]hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]-3-(1H-indol-3-yl)propan-1-one'>EBV</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">HRAS, HRAS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SOS1 ([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=6bvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bvm OCA], [https://pdbe.org/6bvm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bvm RCSB], [https://www.ebi.ac.uk/pdbsum/6bvm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bvm 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=6bvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bvm OCA], [~~http~~://pdbe.org/6bvm PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6bvm RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6bvm PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6bvm ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/RASH_HUMAN RASH_HUMAN]] Defects in HRAS are the cause of faciocutaneoskeletal syndrome (FCSS) [MIM:[~~http~~://omim.org/entry/218040 218040]]. A rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.<ref>PMID:16170316</ref> <ref>PMID:16329078</ref> <ref>PMID:16443854</ref> <ref>PMID:17054105</ref> <ref>PMID:18247425</ref> <ref>PMID:18039947</ref> <ref>PMID:19995790</ref> Defects in HRAS are the cause of congenital myopathy with excess of muscle spindles (CMEMS) [MIM:[~~http~~://omim.org/entry/218040 218040]]. CMEMS is a variant of Costello syndrome.<ref>PMID:17412879</ref> Defects in HRAS may be a cause of susceptibility to Hurthle cell thyroid carcinoma (HCTC) [MIM:[~~http~~://omim.org/entry/607464 607464]]. Hurthle cell thyroid carcinoma accounts for approximately 3% of all thyroid cancers. Although they are classified as variants of follicular neoplasms, they are more often multifocal and somewhat more aggressive and are less likely to take up iodine than are other follicular neoplasms. Note=Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors. Defects in HRAS are a cause of susceptibility to bladder cancer (BLC) [MIM:[~~http~~://omim.org/entry/109800 109800]]. A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas. They begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Note=Defects in HRAS are the cause of oral squamous cell carcinoma (OSCC).<ref>PMID:1459726</ref> Defects in HRAS are the cause of Schimmelpenning-Feuerstein-Mims syndrome (SFM) [MIM:[~~http~~://omim.org/entry/163200 163200]]. A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis.<ref>PMID:22683711</ref> [[http://www.uniprot.org/uniprot/SOS1_HUMAN SOS1_HUMAN]] Defects in SOS1 are the cause of gingival fibromatosis 1 (GGF1) [MIM:[http://omim.org/entry/135300 135300]]; also known as GINGF1. Gingival fibromatosis is a rare overgrowth condition characterized by a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva. GGF1 is usually transmitted as an autosomal dominant trait, although sporadic cases are common.<ref>PMID:11868160</ref> Defects in SOS1 are the cause of Noonan syndrome type 4 (NS4) [MIM:[http://omim.org/entry/610733 610733]]. NS4 is an autosomal dominant 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, NS4 is associated with juvenile myelomonocytic leukemia (JMML). SOS1 mutations engender a high prevalence of pulmonary valve disease; atrial septal defects are less common.<ref>PMID:17143285</ref> <ref>PMID:17143282</ref> <ref>PMID:19020799</ref> <ref>PMID:19438935</ref> <ref>PMID:20683980</ref> <ref>PMID:20673819</ref> <ref>PMID:19953625</ref> <ref>PMID:21387466</ref>	+	[https://www.uniprot.org/uniprot/RASH_HUMAN RASH_HUMAN] Defects in HRAS are the cause of faciocutaneoskeletal syndrome (FCSS) [MIM:[https://omim.org/entry/218040 218040]. A rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.<ref>PMID:16170316</ref> <ref>PMID:16329078</ref> <ref>PMID:16443854</ref> <ref>PMID:17054105</ref> <ref>PMID:18247425</ref> <ref>PMID:18039947</ref> <ref>PMID:19995790</ref> Defects in HRAS are the cause of congenital myopathy with excess of muscle spindles (CMEMS) [MIM:[https://omim.org/entry/218040 218040]. CMEMS is a variant of Costello syndrome.<ref>PMID:17412879</ref> Defects in HRAS may be a cause of susceptibility to Hurthle cell thyroid carcinoma (HCTC) [MIM:[https://omim.org/entry/607464 607464]. Hurthle cell thyroid carcinoma accounts for approximately 3% of all thyroid cancers. Although they are classified as variants of follicular neoplasms, they are more often multifocal and somewhat more aggressive and are less likely to take up iodine than are other follicular neoplasms. Note=Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors. Defects in HRAS are a cause of susceptibility to bladder cancer (BLC) [MIM:[https://omim.org/entry/109800 109800]. A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas. They begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Note=Defects in HRAS are the cause of oral squamous cell carcinoma (OSCC).<ref>PMID:1459726</ref> Defects in HRAS are the cause of Schimmelpenning-Feuerstein-Mims syndrome (SFM) [MIM:[https://omim.org/entry/163200 163200]. A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis.<ref>PMID:22683711</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/RASH_HUMAN RASH_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.<ref>PMID:14500341</ref> <ref>PMID:9020151</ref> <ref>PMID:12740440</ref> ~~[[http://www.uniprot.org/uniprot/SOS1_HUMAN SOS1_HUMAN]] Promotes the exchange of Ras-bound GDP by GTP.~~	+	[https://www.uniprot.org/uniprot/RASH_HUMAN RASH_HUMAN] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.<ref>PMID:14500341</ref> <ref>PMID:9020151</ref> <ref>PMID:12740440</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 6bvm" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6bvm" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[GTPase Hras 3D structures\|GTPase Hras 3D structures]]
		+	*[[Son of sevenless\|Son of sevenless]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Abbott, J]]	+	[[Category: Abbott J]]
-	[[Category: Fesik~~, S W~~]]	+	[[Category: Fesik SW]]
-	[[Category: Phan, J]]	+	[[Category: Phan J]]
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Mapk]]~~	+
-	~~[[Category: Oncoprotein]]~~	+
-	~~[[Category: Protein-protein complex]]~~	+
-	~~[[Category: Ra]]~~	+
-	~~[[Category: Signaling protein]]~~	+
-	~~[[Category: So~~]]	+

OCA at 09:06, 1 May 2019

2019-05-01T09:06:07Z

←Older revision		Revision as of 09:06, 1 May 2019
Line 1:		Line 1:

	==Ras:SOS:Ras in complex with a small molecule activator==		==Ras:SOS:Ras in complex with a small molecule activator==
-	<StructureSection load='6bvm' size='340' side='right' caption='[[6bvm]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='6bvm' size='340' side='right'caption='[[6bvm]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6bvm]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BVM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BVM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6bvm]] 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=6BVM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BVM FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EBV:(2S)-2-amino-1-[(3aR,6aS)-5-[(5-chloro-1H-indol-3-yl)methyl]hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]-3-(1H-indol-3-yl)propan-1-one'>EBV</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EBV:(2S)-2-amino-1-[(3aR,6aS)-5-[(5-chloro-1H-indol-3-yl)methyl]hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]-3-(1H-indol-3-yl)propan-1-one'>EBV</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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">HRAS, HRAS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SOS1 ([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=6bvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bvm OCA], [http://pdbe.org/6bvm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bvm RCSB], [http://www.ebi.ac.uk/pdbsum/6bvm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bvm 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=6bvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bvm OCA], [http://pdbe.org/6bvm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bvm RCSB], [http://www.ebi.ac.uk/pdbsum/6bvm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bvm ProSAT]</span></td></tr>
	</table>		</table>
Line 25:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Abbott, J]]		[[Category: Abbott, J]]
	[[Category: Fesik, S W]]		[[Category: Fesik, S W]]

OCA at 05:52, 24 October 2018

2018-10-24T05:52:06Z

←Older revision		Revision as of 05:52, 24 October 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6bvm is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Ras:SOS:Ras in complex with a small molecule activator==
		+	<StructureSection load='6bvm' size='340' side='right' caption='[[6bvm]], [[Resolution\|resolution]] 1.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6bvm]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BVM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BVM FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EBV:(2S)-2-amino-1-[(3aR,6aS)-5-[(5-chloro-1H-indol-3-yl)methyl]hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl]-3-(1H-indol-3-yl)propan-1-one'>EBV</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=6bvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bvm OCA], [http://pdbe.org/6bvm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bvm RCSB], [http://www.ebi.ac.uk/pdbsum/6bvm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bvm ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/RASH_HUMAN RASH_HUMAN]] Defects in HRAS are the cause of faciocutaneoskeletal syndrome (FCSS) [MIM:[http://omim.org/entry/218040 218040]]. A rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.<ref>PMID:16170316</ref> <ref>PMID:16329078</ref> <ref>PMID:16443854</ref> <ref>PMID:17054105</ref> <ref>PMID:18247425</ref> <ref>PMID:18039947</ref> <ref>PMID:19995790</ref> Defects in HRAS are the cause of congenital myopathy with excess of muscle spindles (CMEMS) [MIM:[http://omim.org/entry/218040 218040]]. CMEMS is a variant of Costello syndrome.<ref>PMID:17412879</ref> Defects in HRAS may be a cause of susceptibility to Hurthle cell thyroid carcinoma (HCTC) [MIM:[http://omim.org/entry/607464 607464]]. Hurthle cell thyroid carcinoma accounts for approximately 3% of all thyroid cancers. Although they are classified as variants of follicular neoplasms, they are more often multifocal and somewhat more aggressive and are less likely to take up iodine than are other follicular neoplasms. Note=Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors. Defects in HRAS are a cause of susceptibility to bladder cancer (BLC) [MIM:[http://omim.org/entry/109800 109800]]. A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas. They begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Note=Defects in HRAS are the cause of oral squamous cell carcinoma (OSCC).<ref>PMID:1459726</ref> Defects in HRAS are the cause of Schimmelpenning-Feuerstein-Mims syndrome (SFM) [MIM:[http://omim.org/entry/163200 163200]]. A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis.<ref>PMID:22683711</ref> [[http://www.uniprot.org/uniprot/SOS1_HUMAN SOS1_HUMAN]] Defects in SOS1 are the cause of gingival fibromatosis 1 (GGF1) [MIM:[http://omim.org/entry/135300 135300]]; also known as GINGF1. Gingival fibromatosis is a rare overgrowth condition characterized by a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva. GGF1 is usually transmitted as an autosomal dominant trait, although sporadic cases are common.<ref>PMID:11868160</ref> Defects in SOS1 are the cause of Noonan syndrome type 4 (NS4) [MIM:[http://omim.org/entry/610733 610733]]. NS4 is an autosomal dominant 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, NS4 is associated with juvenile myelomonocytic leukemia (JMML). SOS1 mutations engender a high prevalence of pulmonary valve disease; atrial septal defects are less common.<ref>PMID:17143285</ref> <ref>PMID:17143282</ref> <ref>PMID:19020799</ref> <ref>PMID:19438935</ref> <ref>PMID:20683980</ref> <ref>PMID:20673819</ref> <ref>PMID:19953625</ref> <ref>PMID:21387466</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/RASH_HUMAN RASH_HUMAN]] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.<ref>PMID:14500341</ref> <ref>PMID:9020151</ref> <ref>PMID:12740440</ref> [[http://www.uniprot.org/uniprot/SOS1_HUMAN SOS1_HUMAN]] Promotes the exchange of Ras-bound GDP by GTP.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Deregulated RAS activity, often the result of mutation, is implicated in approximately 30% of all human cancers. Despite this statistic, no clinically successful treatment for RAS-driven tumors has yet been developed. One approach for modulating RAS activity is to target and affect the activity of proteins that interact with RAS, such as the guanine nucleotide exchange factor (GEF) son of sevenless homologue 1 (SOS1). Here, we report on structure-activity relationships (SAR) in an indole series of compounds. Using structure-based design, we systematically explored substitution patterns on the indole nucleus, the pendant amino acid moiety, and the linker unit that connects these two fragments. Best-in-class compounds activate the nucleotide exchange process at submicromolar concentrations in vitro, increase levels of active RAS-GTP in HeLa cells, and elicit signaling changes in the mitogen-activated protein kinase-extracellular regulated kinase (MAPK-ERK) pathway, resulting in a decrease in pERK1/2(T202/Y204) protein levels at higher compound concentrations.

-	~~Authors: Phan, J~~., Abbott, J., ~~Fesik~~, S.W.	+	Discovery of Aminopiperidine Indoles That Activate the Guanine Nucleotide Exchange Factor SOS1 and Modulate RAS Signaling.,Abbott JR, Hodges TR, Daniels RN, Patel PA, Kennedy JP, Howes JE, Akan DT, Burns MC, Sai J, Sobolik T, Beesetty Y, Lee T, Rossanese OW, Phan J, Waterson AG, Fesik SW J Med Chem. 2018 Jul 11. doi: 10.1021/acs.jmedchem.8b00360. PMID:29856609<ref>PMID:29856609</ref>

-	~~Description: Ras:SOS:Ras in complex with~~ a ~~small molecule activator~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Fesik, S.W]]~~	+	<div class="pdbe-citations 6bvm" style="background-color:#fffaf0;"></div>
-	~~[[Category: Phan, J]]~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Abbott, J]]		[[Category: Abbott, J]]
		+	[[Category: Fesik, S W]]
		+	[[Category: Phan, J]]
		+	[[Category: Inhibitor]]
		+	[[Category: Mapk]]
		+	[[Category: Oncoprotein]]
		+	[[Category: Protein-protein complex]]
		+	[[Category: Ra]]
		+	[[Category: Signaling protein]]
		+	[[Category: So]]

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	Authors: Phan, J., Abbott, J., Fesik, S.W.		Authors: Phan, J., Abbott, J., Fesik, S.W.

OCA: Protected "6bvm" [edit=sysop:move=sysop]

2017-12-20T05:04:06Z

Protected "6bvm" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:04, 20 December 2017

OCA: New page: '''Unreleased structure''' The entry 6bvm is ON HOLD Authors: Phan, J., Abbott, J., Fesik, S.W. Description: Ras:SOS:Ras in complex with a small molecule activator [[Category: Unreleas...

2017-12-20T05:04:05Z

New page: '''Unreleased structure''' The entry 6bvm is ON HOLD Authors: Phan, J., Abbott, J., Fesik, S.W. Description: Ras:SOS:Ras in complex with a small molecule activator [[Category: Unreleas...

New page

'''Unreleased structure'''

The entry 6bvm is ON HOLD

Authors: Phan, J., Abbott, J., Fesik, S.W.

Description: Ras:SOS:Ras in complex with a small molecule activator
[[Category: Unreleased Structures]]
[[Category: Fesik, S.W]]
[[Category: Phan, J]]
[[Category: Abbott, J]]