7vxg - Revision history

OCA at 17:33, 29 November 2023

OCA — Wed, 29 Nov 2023 17:33:48 GMT

←Older revision		Revision as of 17:33, 29 November 2023
Line 3:		Line 3:
	<StructureSection load='7vxg' size='340' side='right'caption='[[7vxg]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='7vxg' size='340' side='right'caption='[[7vxg]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7vxg]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VXG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VXG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7vxg]] is a 4 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=7VXG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VXG FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=83Q:6~~-[~~4-(aminomethyl)-4-methyl-piperidin-1-yl]-3-~~[~~2,3-bis(chloranyl)phenyl~~]~~sulfanyl-pyrazin-~~2~~-amine'>83Q</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]] 2.1Å</td></tr>
-	<tr id='~~activity~~'><td class="sblockLbl"><b>~~Activity~~:</b></td><td class="sblockDat"><~~span class~~='~~plainlinks'>[https~~:~~//en.wikipedia.org/wiki/Protein~~-~~tyrosine~~-~~phosphatase Protein~~-~~tyrosine~~-~~phosphatase~~]~~, with EC number [https://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=~~3~~.1.~~3~~.48 3.1.3.48~~] </~~span~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=83Q:6-[4-(aminomethyl)-4-methyl-piperidin-1-yl]-3-[2,3-bis(chloranyl)phenyl]sulfanyl-pyrazin-2-amine'>83Q</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=7vxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vxg OCA], [https://pdbe.org/7vxg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vxg RCSB], [https://www.ebi.ac.uk/pdbsum/7vxg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vxg 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=7vxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vxg OCA], [https://pdbe.org/7vxg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vxg RCSB], [https://www.ebi.ac.uk/pdbsum/7vxg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vxg ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[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>	+	[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 ==
-	[[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>	+	[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 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 7vxg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7vxg" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tyrosine phosphatase 3D structures\|Tyrosine phosphatase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Protein-tyrosine-phosphatase]]~~	+	[[Category: Guo HT]]
-	[[Category: Guo~~, H T~~]]	+	[[Category: Ji XY]]
-	[[Category: Ji~~, X Y~~]]	+	[[Category: Li TH]]
-	[[Category: Li~~, T H]]~~	+
-	~~[[Category: Antitumor protein]]~~	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Protein tyrosine phosphatase]]~~	+
-	~~[[Category: Shp2~~]]	+

OCA at 10:39, 6 April 2022

OCA — Wed, 06 Apr 2022 10:39:54 GMT

←Older revision		Revision as of 10:39, 6 April 2022
Line 1:		Line 1:

	==Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor TK-453==		==Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor TK-453==
-	<StructureSection load='7vxg' size='340' side='right'caption='[[7vxg]]' scene=''>	+	<StructureSection load='7vxg' size='340' side='right'caption='[[7vxg]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VXG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VXG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7vxg]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VXG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VXG FirstGlance]. <br>
-	</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=7vxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vxg OCA], [https://pdbe.org/7vxg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vxg RCSB], [https://www.ebi.ac.uk/pdbsum/7vxg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vxg ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=83Q:6-[4-(aminomethyl)-4-methyl-piperidin-1-yl]-3-[2,3-bis(chloranyl)phenyl]sulfanyl-pyrazin-2-amine'>83Q</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [https://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=7vxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vxg OCA], [https://pdbe.org/7vxg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vxg RCSB], [https://www.ebi.ac.uk/pdbsum/7vxg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vxg ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[[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 ==
		+	[[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;">
		+	== Publication Abstract from PubMed ==
		+	SHP2 is the first oncogenic tyrosine phosphatase encoded by PTPN11, which plays a significant regulatory role in cancer and inflammation-related diseases. Although SHP2 allosteric inhibitors have been used in phase I/II clinical trials for solid tumors, whether SHP2 inhibition alleviates psoriasis remains unclear. Here we expressed and purified SHP2 related proteins, and established an enzyme activity screening system for different conformations of SHP2. We launched an iterative medicinal chemistry program and identified the lead compound, TK-453. Importantly, TK-453 possessed stronger affinity with SHP2 than SHP099, evidenced by the cocrystal structure of SHP2/TK-453, revealing that the additional aryl-S-aryl bridge in TK-453 induces a 1.8 A shift of the dichlorophenyl ring and an approximate 20 degrees deviation of the pyrazine ring plane relative to SHP099. Furthermore, TK-453 significantly ameliorated imiquimod-triggered skin inflammation in mice via inhibition of the IL-23/Th17 axis, proving that SHP2 is a potential therapeutic target for psoriasis.
		+
		+	SHP2 allosteric inhibitor TK-453 alleviates psoriasis-like skin inflammation in mice via inhibition of IL-23/Th17 axis.,Wang M, Li T, Ouyang Z, Tang K, Zhu Y, Song C, Sun H, Yu B, Ji X, Sun Y iScience. 2022 Mar 1;25(4):104009. doi: 10.1016/j.isci.2022.104009. eCollection, 2022 Apr 15. PMID:35310939<ref>PMID:35310939</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7vxg" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Guo HT]]	+	[[Category: Protein-tyrosine-phosphatase]]
-	[[Category: Ji XY]]	+	[[Category: Guo, H T]]
-	[[Category: Li TH]]	+	[[Category: Ji, X Y]]
		+	[[Category: Li, T H]]
		+	[[Category: Antitumor protein]]
		+	[[Category: Complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Protein tyrosine phosphatase]]
		+	[[Category: Shp2]]

OCA at 11:21, 23 March 2022

OCA — Wed, 23 Mar 2022 11:21:56 GMT

←Older revision		Revision as of 11:21, 23 March 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7vxg is ~~ON HOLD~~	+	==Non-receptor Protein Tyrosine Phosphatase SHP2 in Complex with Allosteric Inhibitor TK-453==
-		+	<StructureSection load='7vxg' size='340' side='right'caption='[[7vxg]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VXG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VXG FirstGlance]. <br>
-	~~Description~~:	+	</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=7vxg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vxg OCA], [https://pdbe.org/7vxg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vxg RCSB], [https://www.ebi.ac.uk/pdbsum/7vxg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vxg ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Guo HT]]
		+	[[Category: Ji XY]]
		+	[[Category: Li TH]]

OCA: Protected "7vxg" [edit=sysop:move=sysop]

OCA — Wed, 24 Nov 2021 11:04:33 GMT

Protected "7vxg" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:04, 24 November 2021

OCA: New page: '''Unreleased structure''' The entry 7vxg is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 24 Nov 2021 11:04:32 GMT

New page: '''Unreleased structure''' The entry 7vxg is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7vxg is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]