1bfj - Revision history

OCA at 08:18, 22 May 2024

OCA — Wed, 22 May 2024 08:18:01 GMT

←Older revision		Revision as of 08:18, 22 May 2024
Line 19:		Line 19:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1bfj ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1bfj ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Heterodimeric class IA phosphoinositide 3-kinase (PI 3-kinase) plays a crucial role in a variety of cellular signalling events downstream of a number of cell-surface receptor tyrosine kinases. Activation of the enzyme is effected in part by the binding of two Src homology-2 domains (SH2) of the 85 kDa regulatory subunit to specific phosphotyrosine-containing peptide motifs within activated cytoplasmic receptor domains. The solution structure of the uncomplexed C-terminal SH2 (C-SH2) domain of the p85 alpha subunit of PI 3-kinase has been determined by means of multinuclear, double and triple-resonance NMR experiments and restrained molecular-dynamics simulated-annealing calculations. The solution structure clearly indicates that the uncomplexed C-SH2 domain conforms to the consensus polypeptide fold exhibited by other SH2 domains, with an additional short helical element at the N terminus. In particular, the C-SH2 structure is very similar to both the p85 alpha N-terminal SH2 domain (N-SH2) and the Src SH2 domain with a root mean square difference (rmsd) for 44 C alpha atoms of 1.09 and 0.89 A, respectively. The canonical BC, EF and BG loops are less well-defined by the experimental restraints and show greater variability in the ensemble of C-SH2 conformers. The lower level of definition in these regions may reflect the presence of conformational disorder, an interpretation supported by the absence or broadening of backbone and side-chain NMR resonances for some of these residues. NMR experiments were performed, where C-SH2 was titrated with phosphotyrosine-containing peptides corresponding to p85 alpha recognition sites in the cytoplasmic domain of the platelet-derived growth-factor receptor. The ligand-induced chemical-shift perturbations indicate the amino-acid residues in C-SH2 involved in peptide recognition follow the pattern predicted from homologous complexes. A series of C-SH2 mutants was generated and tested for phosphotyrosine peptide binding by surface plasmon resonance. Mutation of the invariant Arg36 (beta B5) to Met completely abolishes phosphopeptide binding. Mutation of each of Ser38, Ser39 or Lys40 in the BC loop to Ala reduces the affinity of C-SH2 for a cognate phosphopeptide, as does mutation of His93 (BG5) to Asn. These effects are consistent with the involvement of the BC loop and BG loops regions in ligation of phosphopeptide ligands. Mutation of Cys57 (beta D5) in C-SH2 to Ile, the corresponding residue type in the p85 alpha N-SH2 domain, results in a change in peptide binding selectivity of C-SH2 towards that demonstrated by p85 alpha N-SH2. This pattern of p85 alpha phosphopeptide binding specificity is interpreted in terms of a model of the p85 alpha/PDGF-receptor interaction.
		+
		+	Solution structure of the C-terminal SH2 domain of the p85 alpha regulatory subunit of phosphoinositide 3-kinase.,Siegal G, Davis B, Kristensen SM, Sankar A, Linacre J, Stein RC, Panayotou G, Waterfield MD, Driscoll PC J Mol Biol. 1998 Feb 20;276(2):461-78. PMID:9512716<ref>PMID:9512716</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 1bfj" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Phosphoinositide 3-kinase 3D structures\|Phosphoinositide 3-kinase 3D structures]]		*[[Phosphoinositide 3-kinase 3D structures\|Phosphoinositide 3-kinase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 15:32, 13 March 2024

OCA — Wed, 13 Mar 2024 15:32:29 GMT

←Older revision		Revision as of 15:32, 13 March 2024
Line 1:		Line 1:

	==SOLUTION STRUCTURE OF THE C-TERMINAL SH2 DOMAIN OF THE P85ALPHA REGULATORY SUBUNIT OF PHOSPHOINOSITIDE 3-KINASE, NMR, MINIMIZED AVERAGE STRUCTURE==		==SOLUTION STRUCTURE OF THE C-TERMINAL SH2 DOMAIN OF THE P85ALPHA REGULATORY SUBUNIT OF PHOSPHOINOSITIDE 3-KINASE, NMR, MINIMIZED AVERAGE STRUCTURE==
-	<StructureSection load='1bfj' size='340' side='right'caption='[[1bfj~~]], [[NMR_Ensembles_of_Models \| 1 NMR models~~]]' scene=''>	+	<StructureSection load='1bfj' size='340' side='right'caption='[[1bfj]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1bfj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Bovin Bovin~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BFJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BFJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1bfj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BFJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BFJ FirstGlance]. <br>
-	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style~~=~~'overflow: auto; max-height: 3em;'>[[1bfi\|1bfi]]</div~~></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1bfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bfj OCA], [https://pdbe.org/1bfj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bfj RCSB], [https://www.ebi.ac.uk/pdbsum/1bfj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bfj 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=1bfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bfj OCA], [https://pdbe.org/1bfj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bfj RCSB], [https://www.ebi.ac.uk/pdbsum/1bfj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bfj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/P85A_BOVIN P85A_BOVIN]] Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity).	+	[https://www.uniprot.org/uniprot/P85A_BOVIN P85A_BOVIN] Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 19:		Line 19:
	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1bfj ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1bfj ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Heterodimeric class IA phosphoinositide 3-kinase (PI 3-kinase) plays a crucial role in a variety of cellular signalling events downstream of a number of cell-surface receptor tyrosine kinases. Activation of the enzyme is effected in part by the binding of two Src homology-2 domains (SH2) of the 85 kDa regulatory subunit to specific phosphotyrosine-containing peptide motifs within activated cytoplasmic receptor domains. The solution structure of the uncomplexed C-terminal SH2 (C-SH2) domain of the p85 alpha subunit of PI 3-kinase has been determined by means of multinuclear, double and triple-resonance NMR experiments and restrained molecular-dynamics simulated-annealing calculations. The solution structure clearly indicates that the uncomplexed C-SH2 domain conforms to the consensus polypeptide fold exhibited by other SH2 domains, with an additional short helical element at the N terminus. In particular, the C-SH2 structure is very similar to both the p85 alpha N-terminal SH2 domain (N-SH2) and the Src SH2 domain with a root mean square difference (rmsd) for 44 C alpha atoms of 1.09 and 0.89 A, respectively. The canonical BC, EF and BG loops are less well-defined by the experimental restraints and show greater variability in the ensemble of C-SH2 conformers. The lower level of definition in these regions may reflect the presence of conformational disorder, an interpretation supported by the absence or broadening of backbone and side-chain NMR resonances for some of these residues. NMR experiments were performed, where C-SH2 was titrated with phosphotyrosine-containing peptides corresponding to p85 alpha recognition sites in the cytoplasmic domain of the platelet-derived growth-factor receptor. The ligand-induced chemical-shift perturbations indicate the amino-acid residues in C-SH2 involved in peptide recognition follow the pattern predicted from homologous complexes. A series of C-SH2 mutants was generated and tested for phosphotyrosine peptide binding by surface plasmon resonance. Mutation of the invariant Arg36 (beta B5) to Met completely abolishes phosphopeptide binding. Mutation of each of Ser38, Ser39 or Lys40 in the BC loop to Ala reduces the affinity of C-SH2 for a cognate phosphopeptide, as does mutation of His93 (BG5) to Asn. These effects are consistent with the involvement of the BC loop and BG loops regions in ligation of phosphopeptide ligands. Mutation of Cys57 (beta D5) in C-SH2 to Ile, the corresponding residue type in the p85 alpha N-SH2 domain, results in a change in peptide binding selectivity of C-SH2 towards that demonstrated by p85 alpha N-SH2. This pattern of p85 alpha phosphopeptide binding specificity is interpreted in terms of a model of the p85 alpha/PDGF-receptor interaction.
-
-	Solution structure of the C-terminal SH2 domain of the p85 alpha regulatory subunit of phosphoinositide 3-kinase.,Siegal G, Davis B, Kristensen SM, Sankar A, Linacre J, Stein RC, Panayotou G, Waterfield MD, Driscoll PC J Mol Biol. 1998 Feb 20;276(2):461-78. PMID:9512716<ref>PMID:9512716</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1bfj" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Phosphoinositide 3-kinase 3D structures\|Phosphoinositide 3-kinase 3D structures]]		*[[Phosphoinositide 3-kinase 3D structures\|Phosphoinositide 3-kinase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bovin~~]]	+	[[Category: Bos taurus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Davis, B]]	+	[[Category: Davis B]]
-	[[Category: Driscoll~~, P C~~]]	+	[[Category: Driscoll PC]]
-	[[Category: Kristensen~~, S M~~]]	+	[[Category: Kristensen SM]]
-	[[Category: Linacre, J]]	+	[[Category: Linacre J]]
-	[[Category: Panayotou, G]]	+	[[Category: Panayotou G]]
-	[[Category: Sankar, A]]	+	[[Category: Sankar A]]
-	[[Category: Siegal, G]]	+	[[Category: Siegal G]]
-	[[Category: Stein~~, R C~~]]	+	[[Category: Stein RC]]
-	[[Category: Waterfield~~, M D]]~~	+	[[Category: Waterfield MD]]
-	~~[[Category: C terminal sh2 domain]]~~	+
-	~~[[Category: P85alpha]]~~	+
-	~~[[Category: Pi 3-kinase]]~~	+
-	~~[[Category: Sh2 domain~~]]	+

OCA at 10:40, 19 May 2021

OCA — Wed, 19 May 2021 10:40:25 GMT

←Older revision		Revision as of 10:40, 19 May 2021
Line 3:		Line 3:
	<StructureSection load='1bfj' size='340' side='right'caption='[[1bfj]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>		<StructureSection load='1bfj' size='340' side='right'caption='[[1bfj]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1bfj]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Bovin Bovin]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BFJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1BFJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1bfj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BFJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BFJ FirstGlance]. <br>
-	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1bfi\|1bfi]]</td></tr>	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1bfi\|1bfi]]</div></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=1bfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bfj OCA], [~~http~~://pdbe.org/1bfj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1bfj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1bfj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1bfj 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=1bfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bfj OCA], [https://pdbe.org/1bfj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bfj RCSB], [https://www.ebi.ac.uk/pdbsum/1bfj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bfj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/P85A_BOVIN P85A_BOVIN]] Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity).	+	[[https://www.uniprot.org/uniprot/P85A_BOVIN P85A_BOVIN]] Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 30:		Line 30:

	==See Also==		==See Also==
-	*[[Phosphoinositide 3-~~Kinases~~\|Phosphoinositide 3-~~Kinases~~]]	+	*[[Phosphoinositide 3-kinase 3D structures\|Phosphoinositide 3-kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:58, 14 August 2019

OCA — Wed, 14 Aug 2019 17:58:06 GMT

←Older revision		Revision as of 17:58, 14 August 2019
Line 1:		Line 1:

	==SOLUTION STRUCTURE OF THE C-TERMINAL SH2 DOMAIN OF THE P85ALPHA REGULATORY SUBUNIT OF PHOSPHOINOSITIDE 3-KINASE, NMR, MINIMIZED AVERAGE STRUCTURE==		==SOLUTION STRUCTURE OF THE C-TERMINAL SH2 DOMAIN OF THE P85ALPHA REGULATORY SUBUNIT OF PHOSPHOINOSITIDE 3-KINASE, NMR, MINIMIZED AVERAGE STRUCTURE==
-	<StructureSection load='1bfj' size='340' side='right' caption='[[1bfj]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>	+	<StructureSection load='1bfj' size='340' side='right'caption='[[1bfj]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1bfj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BFJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[1bfj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BFJ FirstGlance]. <br>
Line 13:		Line 13:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bf/1bfj_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bf/1bfj_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 28:		Line 28:
	</div>		</div>
	<div class="pdbe-citations 1bfj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1bfj" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]
	== References ==		== References ==
	<references/>		<references/>
Line 33:		Line 36:
	</StructureSection>		</StructureSection>
	[[Category: Bovin]]		[[Category: Bovin]]
		+	[[Category: Large Structures]]
	[[Category: Davis, B]]		[[Category: Davis, B]]
	[[Category: Driscoll, P C]]		[[Category: Driscoll, P C]]

OCA at 10:57, 8 November 2017

OCA — Wed, 08 Nov 2017 10:57:41 GMT

←Older revision		Revision as of 10:57, 8 November 2017
Line 1:		Line 1:
		+
	==SOLUTION STRUCTURE OF THE C-TERMINAL SH2 DOMAIN OF THE P85ALPHA REGULATORY SUBUNIT OF PHOSPHOINOSITIDE 3-KINASE, NMR, MINIMIZED AVERAGE STRUCTURE==		==SOLUTION STRUCTURE OF THE C-TERMINAL SH2 DOMAIN OF THE P85ALPHA REGULATORY SUBUNIT OF PHOSPHOINOSITIDE 3-KINASE, NMR, MINIMIZED AVERAGE STRUCTURE==
	<StructureSection load='1bfj' size='340' side='right' caption='[[1bfj]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>		<StructureSection load='1bfj' size='340' side='right' caption='[[1bfj]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>
Line 4:		Line 5:
	<table><tr><td colspan='2'>[[1bfj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BFJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[1bfj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BFJ FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1bfi\|1bfi]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1bfi\|1bfi]]</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=1bfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bfj OCA], [http://pdbe.org/1bfj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1bfj RCSB], [http://www.ebi.ac.uk/pdbsum/1bfj 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=1bfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bfj OCA], [http://pdbe.org/1bfj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1bfj RCSB], [http://www.ebi.ac.uk/pdbsum/1bfj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1bfj ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 27:		Line 28:
	</div>		</div>
	<div class="pdbe-citations 1bfj" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1bfj" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 14:56, 7 February 2016

OCA — Sun, 07 Feb 2016 14:56:54 GMT

←Older revision		Revision as of 14:56, 7 February 2016
Line 16:		Line 16:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1bfj ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 02:34, 10 September 2015

OCA — Thu, 10 Sep 2015 02:34:36 GMT

←Older revision		Revision as of 02:34, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='1bfj' size='340' side='right' caption='[[1bfj]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>		<StructureSection load='1bfj' size='340' side='right' caption='[[1bfj]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1bfj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Bos_taurus Bos taurus~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BFJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1bfj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BFJ FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1bfi\|1bfi]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1bfi\|1bfi]]</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=1bfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bfj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1bfj RCSB], [http://www.ebi.ac.uk/pdbsum/1bfj 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=1bfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bfj OCA], [http://pdbe.org/1bfj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1bfj RCSB], [http://www.ebi.ac.uk/pdbsum/1bfj PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 26:		Line 26:
	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 1bfj" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 33:		Line 34:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Bos taurus~~]]	+	[[Category: Bovin]]
	[[Category: Davis, B]]		[[Category: Davis, B]]
	[[Category: Driscoll, P C]]		[[Category: Driscoll, P C]]

OCA at 16:03, 24 December 2014

OCA — Wed, 24 Dec 2014 16:03:51 GMT

←Older revision		Revision as of 16:03, 24 December 2014
Line 6:		Line 6:
	<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=1bfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bfj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1bfj RCSB], [http://www.ebi.ac.uk/pdbsum/1bfj 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=1bfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bfj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1bfj RCSB], [http://www.ebi.ac.uk/pdbsum/1bfj PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/P85A_BOVIN P85A_BOVIN]] Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (By similarity).
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]

OCA at 10:53, 22 December 2014

OCA — Mon, 22 Dec 2014 10:53:26 GMT

←Older revision		Revision as of 10:53, 22 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1bfj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BFJ FirstGlance]. <br>		<table><tr><td colspan='2'>[[1bfj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BFJ FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1bfi\|1bfi]]</td></tr>	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1bfi\|1bfi]]</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bfj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1bfj RCSB], [http://www.ebi.ac.uk/pdbsum/1bfj 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=1bfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bfj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1bfj RCSB], [http://www.ebi.ac.uk/pdbsum/1bfj PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 32:		Line 32:
	</StructureSection>		</StructureSection>
	[[Category: Bos taurus]]		[[Category: Bos taurus]]
-	[[Category: Davis, B.]]	+	[[Category: Davis, B]]
-	[[Category: Driscoll, P C.]]	+	[[Category: Driscoll, P C]]
-	[[Category: Kristensen, S M.]]	+	[[Category: Kristensen, S M]]
-	[[Category: Linacre, J.]]	+	[[Category: Linacre, J]]
-	[[Category: Panayotou, G.]]	+	[[Category: Panayotou, G]]
-	[[Category: Sankar, A.]]	+	[[Category: Sankar, A]]
-	[[Category: Siegal, G.]]	+	[[Category: Siegal, G]]
-	[[Category: Stein, R C.]]	+	[[Category: Stein, R C]]
-	[[Category: Waterfield, M D.]]	+	[[Category: Waterfield, M D]]
	[[Category: C terminal sh2 domain]]		[[Category: C terminal sh2 domain]]
	[[Category: P85alpha]]		[[Category: P85alpha]]
	[[Category: Pi 3-kinase]]		[[Category: Pi 3-kinase]]
	[[Category: Sh2 domain]]		[[Category: Sh2 domain]]

OCA at 04:15, 3 October 2014

OCA — Fri, 03 Oct 2014 04:15:24 GMT

←Older revision		Revision as of 04:15, 3 October 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1bfj\| PDB=1bfj \| SCENE= }}~~	+	==SOLUTION STRUCTURE OF THE C-TERMINAL SH2 DOMAIN OF THE P85ALPHA REGULATORY SUBUNIT OF PHOSPHOINOSITIDE 3-KINASE, NMR, MINIMIZED AVERAGE STRUCTURE==
-	===SOLUTION STRUCTURE OF THE C-TERMINAL SH2 DOMAIN OF THE P85ALPHA REGULATORY SUBUNIT OF PHOSPHOINOSITIDE 3-KINASE, NMR, MINIMIZED AVERAGE STRUCTURE===	+	<StructureSection load='1bfj' size='340' side='right' caption='[[1bfj]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>
-	~~{{ABSTRACT_PUBMED_9512716}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1bfj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BFJ FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1bfi\|1bfi]]</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bfj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1bfj RCSB], [http://www.ebi.ac.uk/pdbsum/1bfj PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bf/1bfj_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Heterodimeric class IA phosphoinositide 3-kinase (PI 3-kinase) plays a crucial role in a variety of cellular signalling events downstream of a number of cell-surface receptor tyrosine kinases. Activation of the enzyme is effected in part by the binding of two Src homology-2 domains (SH2) of the 85 kDa regulatory subunit to specific phosphotyrosine-containing peptide motifs within activated cytoplasmic receptor domains. The solution structure of the uncomplexed C-terminal SH2 (C-SH2) domain of the p85 alpha subunit of PI 3-kinase has been determined by means of multinuclear, double and triple-resonance NMR experiments and restrained molecular-dynamics simulated-annealing calculations. The solution structure clearly indicates that the uncomplexed C-SH2 domain conforms to the consensus polypeptide fold exhibited by other SH2 domains, with an additional short helical element at the N terminus. In particular, the C-SH2 structure is very similar to both the p85 alpha N-terminal SH2 domain (N-SH2) and the Src SH2 domain with a root mean square difference (rmsd) for 44 C alpha atoms of 1.09 and 0.89 A, respectively. The canonical BC, EF and BG loops are less well-defined by the experimental restraints and show greater variability in the ensemble of C-SH2 conformers. The lower level of definition in these regions may reflect the presence of conformational disorder, an interpretation supported by the absence or broadening of backbone and side-chain NMR resonances for some of these residues. NMR experiments were performed, where C-SH2 was titrated with phosphotyrosine-containing peptides corresponding to p85 alpha recognition sites in the cytoplasmic domain of the platelet-derived growth-factor receptor. The ligand-induced chemical-shift perturbations indicate the amino-acid residues in C-SH2 involved in peptide recognition follow the pattern predicted from homologous complexes. A series of C-SH2 mutants was generated and tested for phosphotyrosine peptide binding by surface plasmon resonance. Mutation of the invariant Arg36 (beta B5) to Met completely abolishes phosphopeptide binding. Mutation of each of Ser38, Ser39 or Lys40 in the BC loop to Ala reduces the affinity of C-SH2 for a cognate phosphopeptide, as does mutation of His93 (BG5) to Asn. These effects are consistent with the involvement of the BC loop and BG loops regions in ligation of phosphopeptide ligands. Mutation of Cys57 (beta D5) in C-SH2 to Ile, the corresponding residue type in the p85 alpha N-SH2 domain, results in a change in peptide binding selectivity of C-SH2 towards that demonstrated by p85 alpha N-SH2. This pattern of p85 alpha phosphopeptide binding specificity is interpreted in terms of a model of the p85 alpha/PDGF-receptor interaction.

-	~~==About this Structure==~~	+	Solution structure of the C-terminal SH2 domain of the p85 alpha regulatory subunit of phosphoinositide 3-kinase.,Siegal G, Davis B, Kristensen SM, Sankar A, Linacre J, Stein RC, Panayotou G, Waterfield MD, Driscoll PC J Mol Biol. 1998 Feb 20;276(2):461-78. PMID:9512716<ref>PMID:9512716</ref>
-	~~[[1bfj]] is a 1 chain~~ structure ~~with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Bos_taurus Bos taurus]~~. ~~Full experimental information is available from [http~~://~~oca~~.~~weizmann~~.ac.il/~~oca-bin/ocashort?id=1BFJ OCA].~~	+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

	==See Also==		==See Also==
	*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]		*[[Phosphoinositide 3-Kinases\|Phosphoinositide 3-Kinases]]
-	*[[Phsphatidylinositol 3-kinase\|Phsphatidylinositol 3-kinase]]	+	== References ==
-		+	<references/>
-	==~~Reference~~==	+	__TOC__
-	<~~ref group="xtra">PMID:009512716<~~/~~ref~~><~~references group="xtra"~~/>	+	</StructureSection>
	[[Category: Bos taurus]]		[[Category: Bos taurus]]
	[[Category: Davis, B.]]		[[Category: Davis, B.]]