4nyj - Revision history

OCA at 17:04, 20 September 2023

OCA — Wed, 20 Sep 2023 17:04:56 GMT

←Older revision		Revision as of 17:04, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4nyj]] 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=4NYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NYJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[4nyj]] 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=4NYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NYJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PZ:N-[1-(1H-INDOL-3-YLMETHYL)PIPERIDIN-4-YL]GLYCINAMIDE'>2PZ</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</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]] 2.8522Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PZ:N-[1-(1H-INDOL-3-YLMETHYL)PIPERIDIN-4-YL]GLYCINAMIDE'>2PZ</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</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=4nyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nyj OCA], [https://pdbe.org/4nyj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nyj RCSB], [https://www.ebi.ac.uk/pdbsum/4nyj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nyj 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=4nyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nyj OCA], [https://pdbe.org/4nyj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nyj RCSB], [https://www.ebi.ac.uk/pdbsum/4nyj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nyj ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:46, 18 January 2023

OCA — Wed, 18 Jan 2023 08:46:21 GMT

←Older revision		Revision as of 08:46, 18 January 2023
Line 1:		Line 1:

	==Approach for Targeting Ras with Small Molecules that Activate SOS-Mediated Nucleotide Exchange==		==Approach for Targeting Ras with Small Molecules that Activate SOS-Mediated Nucleotide Exchange==
-	<StructureSection load='4nyj' size='340' side='right' caption='[[4nyj]], [[Resolution\|resolution]] 2.85Å' scene=''>	+	<StructureSection load='4nyj' size='340' side='right'caption='[[4nyj]], [[Resolution\|resolution]] 2.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4nyj]] 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=4NYJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4NYJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4nyj]] 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=4NYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NYJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2PZ:N-[1-(1H-INDOL-3-YLMETHYL)PIPERIDIN-4-YL]GLYCINAMIDE'>2PZ</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</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=2PZ:N-[1-(1H-INDOL-3-YLMETHYL)PIPERIDIN-4-YL]GLYCINAMIDE'>2PZ</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4nyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nyj OCA], [https://pdbe.org/4nyj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nyj RCSB], [https://www.ebi.ac.uk/pdbsum/4nyj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nyj 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=4nyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nyj OCA], [~~http~~://pdbe.org/4nyj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4nyj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4nyj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4nyj 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 21:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4nyj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4nyj" 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: ~~Burns, M C~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Fesik, S W~~]]	+	[[Category: Burns MC]]
-	[[Category: ~~Phan, J~~]]	+	[[Category: Fesik SW]]
-	[[Category: ~~Sun, Q~~]]	+	[[Category: Phan J]]
-	[[Category: ~~Cytosol]]~~	+	[[Category: Sun Q]]
-	~~[[Category: Gtpase]]~~	+
-	~~[[Category: Pi3k]]~~	+
-	~~[[Category: Raf]]~~	+
-	~~[[Category: Ralgd]]~~	+
-	~~[[Category: Signaling protein]]~~	+
-	~~[[Category: Signaling transduction~~]]	+

OCA at 14:22, 15 November 2017

OCA — Wed, 15 Nov 2017 14:22:28 GMT

←Older revision		Revision as of 14:22, 15 November 2017
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4nyj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4nyj" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[GTPase HRas\|GTPase HRas]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:06, 11 August 2016

OCA — Thu, 11 Aug 2016 16:06:24 GMT

←Older revision		Revision as of 16:06, 11 August 2016
Line 1:		Line 1:
		+
	==Approach for Targeting Ras with Small Molecules that Activate SOS-Mediated Nucleotide Exchange==		==Approach for Targeting Ras with Small Molecules that Activate SOS-Mediated Nucleotide Exchange==
	<StructureSection load='4nyj' size='340' side='right' caption='[[4nyj]], [[Resolution\|resolution]] 2.85Å' scene=''>		<StructureSection load='4nyj' size='340' side='right' caption='[[4nyj]], [[Resolution\|resolution]] 2.85Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2PZ:N-[1-(1H-INDOL-3-YLMETHYL)PIPERIDIN-4-YL]GLYCINAMIDE'>2PZ</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</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=2PZ:N-[1-(1H-INDOL-3-YLMETHYL)PIPERIDIN-4-YL]GLYCINAMIDE'>2PZ</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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='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=4nyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nyj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nyj RCSB], [http://www.ebi.ac.uk/pdbsum/4nyj 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=4nyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nyj OCA], [http://pdbe.org/4nyj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nyj RCSB], [http://www.ebi.ac.uk/pdbsum/4nyj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nyj ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	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 4nyj" style="background-color:#fffaf0;"></div>

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

OCA at 10:13, 20 January 2015

OCA — Tue, 20 Jan 2015 10:13:23 GMT

←Older revision		Revision as of 10:13, 20 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4nyj\| PDB=4nyj \| SCENE= }}~~	+	==Approach for Targeting Ras with Small Molecules that Activate SOS-Mediated Nucleotide Exchange==
-	===Approach for Targeting Ras with Small Molecules that Activate SOS-Mediated Nucleotide Exchange===	+	<StructureSection load='4nyj' size='340' side='right' caption='[[4nyj]], [[Resolution\|resolution]] 2.85Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24550516}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4nyj]] 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=4NYJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NYJ FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2PZ:N-[1-(1H-INDOL-3-YLMETHYL)PIPERIDIN-4-YL]GLYCINAMIDE'>2PZ</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4nyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nyj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nyj RCSB], [http://www.ebi.ac.uk/pdbsum/4nyj PDBsum]</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>		[[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 ==
-	==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.		[[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 ==
		+	Aberrant activation of the small GTPase Ras by oncogenic mutation or constitutively active upstream receptor tyrosine kinases results in the deregulation of cellular signals governing growth and survival in approximately 30% of all human cancers. However, the discovery of potent inhibitors of Ras has been difficult to achieve. Here, we report the identification of small molecules that bind to a unique pocket on the Ras:Son of Sevenless (SOS):Ras complex, increase the rate of SOS-catalyzed nucleotide exchange in vitro, and modulate Ras signaling pathways in cells. X-ray crystallography of Ras:SOS:Ras in complex with these molecules reveals that the compounds bind in a hydrophobic pocket in the CDC25 domain of SOS adjacent to the Switch II region of Ras. The structure-activity relationships exhibited by these compounds can be rationalized on the basis of multiple X-ray cocrystal structures. Mutational analyses confirmed the functional relevance of this binding site and showed it to be essential for compound activity. These molecules increase Ras-GTP levels and disrupt MAPK and PI3K signaling in cells at low micromolar concentrations. These small molecules represent tools to study the acute activation of Ras and highlight a pocket on SOS that may be exploited to modulate Ras signaling.

-	~~==About this Structure==~~	+	Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange.,Burns MC, Sun Q, Daniels RN, Camper D, Kennedy JP, Phan J, Olejniczak ET, Lee T, Waterson AG, Rossanese OW, Fesik SW Proc Natl Acad Sci U S A. 2014 Mar 4;111(9):3401-6. doi: 10.1073/pnas.1315798111., Epub 2014 Feb 18. PMID:24550516<ref>PMID:24550516</ref>
-	~~[[4nyj]] is a 3 chain structure~~. ~~Full crystallographic information is available from [http~~:/~~/oca~~.~~weizmann~~.ac.il/~~oca-bin~~/~~ocashort?id=4NYJ OCA]~~.	+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

	==See Also==		==See Also==
	*[[GTPase HRas\|GTPase HRas]]		*[[GTPase HRas\|GTPase HRas]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:024550516</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
-	[[Category: Burns, M C.]]	+	</StructureSection>
-	[[Category: Fesik, S W.]]	+	[[Category: Human]]
-	[[Category: Phan, J.]]	+	[[Category: Burns, M C]]
-	[[Category: Sun, Q.]]	+	[[Category: Fesik, S W]]
		+	[[Category: Phan, J]]
		+	[[Category: Sun, Q]]
	[[Category: Cytosol]]		[[Category: Cytosol]]
	[[Category: Gtpase]]		[[Category: Gtpase]]

OCA at 10:02, 19 March 2014

OCA — Wed, 19 Mar 2014 10:02:29 GMT

←Older revision		Revision as of 10:02, 19 March 2014
Line 11:		Line 11:
	==About this Structure==		==About this Structure==
	[[4nyj]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NYJ OCA].		[[4nyj]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NYJ OCA].
		+
		+	==See Also==
		+	*[[GTPase HRas\|GTPase HRas]]

	==Reference==		==Reference==

OCA at 13:34, 12 March 2014

OCA — Wed, 12 Mar 2014 13:34:27 GMT

←Older revision		Revision as of 13:34, 12 March 2014
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4nyj\| PDB=4nyj \| SCENE= }}
		+	===Approach for Targeting Ras with Small Molecules that Activate SOS-Mediated Nucleotide Exchange===
		+	{{ABSTRACT_PUBMED_24550516}}

-	~~The~~ entry ~~4nyj~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	==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>

-	~~Authors~~: ~~Burns, M~~.C.~~, Sun, Q~~.~~, Phan, J~~.~~, Fesik, S~~.W.	+	==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.

-	~~Description~~: ~~Approach for Targeting Ras with Small Molecules that Activate SOS~~-~~Mediated Nucleotide Exchange~~	+	==About this Structure==
		+	[[4nyj]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NYJ OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:024550516</ref><references group="xtra"/><references/>
		+	[[Category: Burns, M C.]]
		+	[[Category: Fesik, S W.]]
		+	[[Category: Phan, J.]]
		+	[[Category: Sun, Q.]]
		+	[[Category: Cytosol]]
		+	[[Category: Gtpase]]
		+	[[Category: Pi3k]]
		+	[[Category: Raf]]
		+	[[Category: Ralgd]]
		+	[[Category: Signaling protein]]
		+	[[Category: Signaling transduction]]

OCA at 04:48, 13 February 2014

OCA — Thu, 13 Feb 2014 04:48:54 GMT

←Older revision		Revision as of 04:48, 13 February 2014
Line 1:		Line 1:
-	~~WITHDRAWN:~~ The ~~PDB~~ entry ~~4NYJ was withdrawn~~.	+	'''Unreleased structure'''
		+
		+	The entry 4nyj is ON HOLD until Paper Publication
		+
		+	Authors: Burns, M.C., Sun, Q., Phan, J., Fesik, S.W.
		+
		+	Description: Approach for Targeting Ras with Small Molecules that Activate SOS-Mediated Nucleotide Exchange

OCA at 10:54, 5 February 2014

OCA — Wed, 05 Feb 2014 10:54:06 GMT

←Older revision		Revision as of 10:54, 5 February 2014
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	WITHDRAWN: The PDB entry 4NYJ was withdrawn.
-		+
-	The entry ~~4nyj is ON HOLD~~	+
-		+
-	~~Authors: Burns, M~~.~~C., Sun, Q., Phan, J., Fesik, S.W.~~	+
-		+
-	~~Description: Approach for Targeting Ras with Small Molecules that Activate SOS-Mediated Nucleotide Exchange~~	+

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

OCA — Wed, 18 Dec 2013 09:27:30 GMT

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

←Older revision

Revision as of 09:27, 18 December 2013