6cms - Revision history

OCA at 15:07, 4 October 2023

OCA — Wed, 04 Oct 2023 15:07:31 GMT

←Older revision		Revision as of 15:07, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='6cms' size='340' side='right'caption='[[6cms]], [[Resolution\|resolution]] 2.68Å' scene=''>		<StructureSection load='6cms' size='340' side='right'caption='[[6cms]], [[Resolution\|resolution]] 2.68Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6cms]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CMS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6CMS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6cms]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CMS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CMS FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=5OD:6-(4-AZANYL-4-METHYL-PIPERIDIN-1-YL)-3~~-[~~2,3-BIS(CHLORANYL)PHENYL~~]~~PYRAZIN-~~2~~-AMINE'>5OD</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]] 2.68Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>PTPN11, PTP2C, SHPTP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&~~id~~=9606 HUMAN])</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5OD:6-(4-AZANYL-4-METHYL-PIPERIDIN-1-YL)-3-[2,3-BIS(CHLORANYL)PHENYL]PYRAZIN-2-AMINE'>5OD</scene></td></tr>
-	~~<tr id='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[http~~:~~//en.wikipedia.org/wiki/Protein~~-~~tyrosine~~-~~phosphatase Protein~~-~~tyrosine~~-~~phosphatase], with EC number [http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=3.~~1.3~~.48~~ 3~~.1.3.48~~] </~~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=6cms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cms OCA], [https://pdbe.org/6cms PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cms RCSB], [https://www.ebi.ac.uk/pdbsum/6cms PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cms 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=6cms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cms OCA], [~~http~~://pdbe.org/6cms PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6cms RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6cms PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6cms ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN]] Defects in PTPN11 are the cause of LEOPARD syndrome type 1 (LEOPARD1) [MIM:[~~http~~://omim.org/entry/151100 151100]]. It is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness.<ref>PMID:12058348</ref> <ref>PMID:14961557</ref> <ref>PMID:15389709</ref> <ref>PMID:15520399</ref> <ref>PMID:15121796</ref> <ref>PMID:15690106</ref> <ref>PMID:16679933</ref> Defects in PTPN11 are the cause of Noonan syndrome type 1 (NS1) [MIM:[~~http~~://omim.org/entry/163950 163950]]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. Some patients with Noonan syndrome type 1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villomoduolar synovitis (PVNS) when occurring in the jaw or joints. Note=Mutations in PTPN11 account for more than 50% of the cases. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS1 inheritance is autosomal dominant.<ref>PMID:11704759</ref> <ref>PMID:11992261</ref> <ref>PMID:12325025</ref> <ref>PMID:12161469</ref> <ref>PMID:12529711</ref> <ref>PMID:12634870</ref> <ref>PMID:12739139</ref> <ref>PMID:12960218</ref> <ref>PMID:12717436</ref> <ref>PMID:15384080</ref> <ref>PMID:15948193</ref> <ref>PMID:19020799</ref> Defects in PTPN11 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[~~http~~://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor.<ref>PMID:12717436</ref> Defects in PTPN11 are a cause of metachondromatosis (MC) [MIM:[~~http~~://omim.org/entry/156250 156250]]. It is a skeletal disorder with radiologic fetarures of both multiple exostoses and Ollier disease, characterized by the presence of multiple enchondromas and osteochondroma-like lesions.<ref>PMID:20577567</ref>	+	[https://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN] Defects in PTPN11 are the cause of LEOPARD syndrome type 1 (LEOPARD1) [MIM:[https://omim.org/entry/151100 151100]. It is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness.<ref>PMID:12058348</ref> <ref>PMID:14961557</ref> <ref>PMID:15389709</ref> <ref>PMID:15520399</ref> <ref>PMID:15121796</ref> <ref>PMID:15690106</ref> <ref>PMID:16679933</ref> Defects in PTPN11 are the cause of Noonan syndrome type 1 (NS1) [MIM:[https://omim.org/entry/163950 163950]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. Some patients with Noonan syndrome type 1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villomoduolar synovitis (PVNS) when occurring in the jaw or joints. Note=Mutations in PTPN11 account for more than 50% of the cases. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS1 inheritance is autosomal dominant.<ref>PMID:11704759</ref> <ref>PMID:11992261</ref> <ref>PMID:12325025</ref> <ref>PMID:12161469</ref> <ref>PMID:12529711</ref> <ref>PMID:12634870</ref> <ref>PMID:12739139</ref> <ref>PMID:12960218</ref> <ref>PMID:12717436</ref> <ref>PMID:15384080</ref> <ref>PMID:15948193</ref> <ref>PMID:19020799</ref> Defects in PTPN11 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[https://omim.org/entry/607785 607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor.<ref>PMID:12717436</ref> Defects in PTPN11 are a cause of metachondromatosis (MC) [MIM:[https://omim.org/entry/156250 156250]. It is a skeletal disorder with radiologic fetarures of both multiple exostoses and Ollier disease, characterized by the presence of multiple enchondromas and osteochondroma-like lesions.<ref>PMID:20577567</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN]] Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Dephosphorylates ROCK2 at Tyr-722 resulting in stimulatation of its RhoA binding activity.<ref>PMID:10655584</ref> <ref>PMID:18829466</ref> <ref>PMID:18559669</ref>	+	[https://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN] Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Dephosphorylates ROCK2 at Tyr-722 resulting in stimulatation of its RhoA binding activity.<ref>PMID:10655584</ref> <ref>PMID:18829466</ref> <ref>PMID:18559669</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 6cms" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6cms" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tyrosine phosphatase 3D structures\|Tyrosine phosphatase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Protein-tyrosine-phosphatase]]~~	+	[[Category: Kern D]]
-	[[Category: Kern, D]]	+	[[Category: Marko I]]
-	[[Category: Marko, I]]	+	[[Category: Padua RAP]]
-	[[Category: Padua~~, R A.P~~]]	+	[[Category: Pitsawong W]]
-	[[Category: Pitsawong, W]]	+	[[Category: Sun Y]]
-	[[Category: Sun, Y]]	+
-	~~[[Category: Active mutant]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Inactive state]]~~	+
-	~~[[Category: Protein tyrosine phosphatase]]~~	+
-	~~[[Category: Src homology domain 2~~]]	+

OCA at 06:41, 17 April 2019

OCA — Wed, 17 Apr 2019 06:41:58 GMT

←Older revision		Revision as of 06:41, 17 April 2019
Line 1:		Line 1:

	==Closed structure of active SHP2 mutant E76K bound to SHP099 inhibitor==		==Closed structure of active SHP2 mutant E76K bound to SHP099 inhibitor==
-	<StructureSection load='6cms' size='340' side='right' caption='[[6cms]], [[Resolution\|resolution]] 2.68Å' scene=''>	+	<StructureSection load='6cms' size='340' side='right'caption='[[6cms]], [[Resolution\|resolution]] 2.68Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6cms]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CMS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CMS FirstGlance]. <br>		<table><tr><td colspan='2'>[[6cms]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CMS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CMS FirstGlance]. <br>
Line 27:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Protein-tyrosine-phosphatase]]		[[Category: Protein-tyrosine-phosphatase]]
	[[Category: Kern, D]]		[[Category: Kern, D]]

OCA at 08:29, 21 February 2019

OCA — Thu, 21 Feb 2019 08:29:59 GMT

←Older revision		Revision as of 08:29, 21 February 2019
Line 3:		Line 3:
	<StructureSection load='6cms' size='340' side='right' caption='[[6cms]], [[Resolution\|resolution]] 2.68Å' scene=''>		<StructureSection load='6cms' size='340' side='right' caption='[[6cms]], [[Resolution\|resolution]] 2.68Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6cms]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CMS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CMS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6cms]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CMS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CMS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5OD:6-(4-AZANYL-4-METHYL-PIPERIDIN-1-YL)-3-[2,3-BIS(CHLORANYL)PHENYL]PYRAZIN-2-AMINE'>5OD</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5OD:6-(4-AZANYL-4-METHYL-PIPERIDIN-1-YL)-3-[2,3-BIS(CHLORANYL)PHENYL]PYRAZIN-2-AMINE'>5OD</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PTPN11, PTP2C, SHPTP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </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=6cms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cms OCA], [http://pdbe.org/6cms PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cms RCSB], [http://www.ebi.ac.uk/pdbsum/6cms PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cms 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=6cms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cms OCA], [http://pdbe.org/6cms PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cms RCSB], [http://www.ebi.ac.uk/pdbsum/6cms PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cms ProSAT]</span></td></tr>
Line 25:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Protein-tyrosine-phosphatase]]		[[Category: Protein-tyrosine-phosphatase]]
	[[Category: Kern, D]]		[[Category: Kern, D]]

OCA at 08:14, 14 November 2018

OCA — Wed, 14 Nov 2018 08:14:17 GMT

←Older revision		Revision as of 08:14, 14 November 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The entry ~~6cms~~ is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Closed structure of active SHP2 mutant E76K bound to SHP099 inhibitor==
		+	<StructureSection load='6cms' size='340' side='right' caption='[[6cms]], [[Resolution\|resolution]] 2.68Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6cms]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CMS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CMS FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5OD:6-(4-AZANYL-4-METHYL-PIPERIDIN-1-YL)-3-[2,3-BIS(CHLORANYL)PHENYL]PYRAZIN-2-AMINE'>5OD</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </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=6cms FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cms OCA], [http://pdbe.org/6cms PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cms RCSB], [http://www.ebi.ac.uk/pdbsum/6cms PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cms ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN]] Defects in PTPN11 are the cause of LEOPARD syndrome type 1 (LEOPARD1) [MIM:[http://omim.org/entry/151100 151100]]. It is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness.<ref>PMID:12058348</ref> <ref>PMID:14961557</ref> <ref>PMID:15389709</ref> <ref>PMID:15520399</ref> <ref>PMID:15121796</ref> <ref>PMID:15690106</ref> <ref>PMID:16679933</ref> Defects in PTPN11 are the cause of Noonan syndrome type 1 (NS1) [MIM:[http://omim.org/entry/163950 163950]]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. Some patients with Noonan syndrome type 1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villomoduolar synovitis (PVNS) when occurring in the jaw or joints. Note=Mutations in PTPN11 account for more than 50% of the cases. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS1 inheritance is autosomal dominant.<ref>PMID:11704759</ref> <ref>PMID:11992261</ref> <ref>PMID:12325025</ref> <ref>PMID:12161469</ref> <ref>PMID:12529711</ref> <ref>PMID:12634870</ref> <ref>PMID:12739139</ref> <ref>PMID:12960218</ref> <ref>PMID:12717436</ref> <ref>PMID:15384080</ref> <ref>PMID:15948193</ref> <ref>PMID:19020799</ref> Defects in PTPN11 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[http://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor.<ref>PMID:12717436</ref> Defects in PTPN11 are a cause of metachondromatosis (MC) [MIM:[http://omim.org/entry/156250 156250]]. It is a skeletal disorder with radiologic fetarures of both multiple exostoses and Ollier disease, characterized by the presence of multiple enchondromas and osteochondroma-like lesions.<ref>PMID:20577567</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PTN11_HUMAN PTN11_HUMAN]] Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. Dephosphorylates ROCK2 at Tyr-722 resulting in stimulatation of its RhoA binding activity.<ref>PMID:10655584</ref> <ref>PMID:18829466</ref> <ref>PMID:18559669</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Protein tyrosine phosphatase SHP2 functions as a key regulator of cell cycle control, and activating mutations cause several cancers. Here, we dissect the energy landscape of wild-type SHP2 and the oncogenic mutation E76K. NMR spectroscopy and X-ray crystallography reveal that wild-type SHP2 exchanges between closed, inactive and open, active conformations. E76K mutation shifts this equilibrium toward the open state. The previously unknown open conformation is characterized, including the active-site WPD loop in the inward and outward conformations. Binding of the allosteric inhibitor SHP099 to E76K mutant, despite much weaker, results in an identical structure as the wild-type complex. A conformational selection to the closed state reduces drug affinity which, combined with E76K's much higher activity, demands significantly greater SHP099 concentrations to restore wild-type activity levels. The differences in structural ensembles and drug-binding kinetics of cancer-associated SHP2 forms may stimulate innovative ideas for developing more potent inhibitors for activated SHP2 mutants.

-	~~Authors~~:	+	Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2.,Padua RAP, Sun Y, Marko I, Pitsawong W, Stiller JB, Otten R, Kern D Nat Commun. 2018 Oct 30;9(1):4507. doi: 10.1038/s41467-018-06814-w. PMID:30375376<ref>PMID:30375376</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6cms" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Protein-tyrosine-phosphatase]]
		+	[[Category: Kern, D]]
		+	[[Category: Marko, I]]
		+	[[Category: Padua, R A.P]]
		+	[[Category: Pitsawong, W]]
		+	[[Category: Sun, Y]]
		+	[[Category: Active mutant]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Inactive state]]
		+	[[Category: Protein tyrosine phosphatase]]
		+	[[Category: Src homology domain 2]]

OCA at 04:38, 4 April 2018

OCA — Wed, 04 Apr 2018 04:38:46 GMT

←Older revision		Revision as of 04:38, 4 April 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6cms is ON HOLD	+	The entry 6cms is ON HOLD until Paper Publication

	Authors:		Authors:

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

OCA — Wed, 14 Mar 2018 05:11:12 GMT

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

←Older revision

Revision as of 05:11, 14 March 2018

OCA: New page: '''Unreleased structure''' The entry 6cms is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 14 Mar 2018 05:11:11 GMT

New page: '''Unreleased structure''' The entry 6cms is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6cms is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]