5bug - Revision history

OCA at 11:17, 10 January 2024

2024-01-10T11:17:16Z

← Older revision		Revision as of 11:17, 10 January 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5bug]] 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=5BUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BUG FirstGlance]. <br>		<table><tr><td colspan='2'>[[5bug]] 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=5BUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BUG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</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]] 2.4Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</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=5bug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bug OCA], [https://pdbe.org/5bug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bug RCSB], [https://www.ebi.ac.uk/pdbsum/5bug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bug 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=5bug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bug OCA], [https://pdbe.org/5bug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bug RCSB], [https://www.ebi.ac.uk/pdbsum/5bug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bug ProSAT]</span></td></tr>
	</table>		</table>

OCA at 06:08, 7 June 2023

2023-06-07T06:08:39Z

← Older revision		Revision as of 06:08, 7 June 2023
Line 1:		Line 1:

	==Crystal structure of human phosphatase PTEN oxidized by H2O2==		==Crystal structure of human phosphatase PTEN oxidized by H2O2==
	<StructureSection load='5bug' size='340' side='right' caption='[[5bug]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='5bug' size='340' side='right'caption='[[5bug]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5bug]] is a 4 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=5BUG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5BUG FirstGlance]. <br>		<table><tr><td colspan='2'>[[5bug]] 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=5BUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BUG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene>~~</td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PTEN, MMAC1, TEP1 ([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=5bug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bug OCA], [https://pdbe.org/5bug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bug RCSB], [https://www.ebi.ac.uk/pdbsum/5bug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bug 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=5bug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bug OCA], [~~http~~://pdbe.org/5bug PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5bug RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5bug PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5bug ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[~~[http~~://www.uniprot.org/uniprot/PTEN_HUMAN PTEN_HUMAN]] Defects in PTEN are a cause of Cowden disease (CD) [MIM:[~~http~~://omim.org/entry/158350 158350]]; also known as Cowden syndrome (CS). CD is an autosomal dominant cancer predisposition syndrome associated with elevated risk for tumors of the breast, thyroid and skin. The predominant phenotype for CD is multiple hamartoma syndrome, in many organ systems including the breast (70% of CD patients), thyroid (40-60%), skin, CNS (40%), gastrointestinal tract. Affected individuals are at an increased risk of both breast and thyroid cancers. Trichilemmomas (benign tumors of the hair follicle infundibulum), and mucocutaneous papillomatosis (99%) are hallmarks of CD.<ref>PMID:9256433</ref> <ref>PMID:9811831</ref> <ref>PMID:9345101</ref> <ref>PMID:9399897</ref> <ref>PMID:9259288</ref> <ref>PMID:9140396</ref> <ref>PMID:9797362</ref> <ref>PMID:9600246</ref> <ref>PMID:9467011</ref> <ref>PMID:9735393</ref> <ref>PMID:9832031</ref> <ref>PMID:9425889</ref> <ref>PMID:9915974</ref> <ref>PMID:10051160</ref> <ref>PMID:10234502</ref> <ref>PMID:10866302</ref> <ref>PMID:11230179</ref> <ref>PMID:11494117</ref> Defects in PTEN are the cause of Lhermitte-Duclos disease (LDD) [MIM:[~~http~~://omim.org/entry/158350 158350]]; also known as cerebelloparenchymal disorder VI. LDD is characterized by dysplastic gangliocytoma of the cerebellum which often results in cerebellar signs and seizures. LDD and CD seem to be the same entity, and are considered as hamartoma-neoplasia syndromes. Defects in PTEN are a cause of Bannayan-Zonana syndrome (BZS) [MIM:[~~http~~://omim.org/entry/153480 153480]]; also known as Ruvalcaba-Myhre-Smith syndrome (RMSS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS). In BZS there seems not to be an increased risk of malignancy. It has a partial clinical overlap with CD. BZS is characterized by the classic triad of macrocephaly, lipomatosis and pigmented macules of the gland penis.<ref>PMID:9467011</ref> <ref>PMID:10866302</ref> <ref>PMID:11494117</ref> <ref>PMID:9241266</ref> <ref>PMID:10400993</ref> Defects in PTEN are a cause of head and neck squamous cell carcinomas (HNSCC) [MIM:[~~http~~://omim.org/entry/275355 275355]]; also known as squamous cell carcinoma of the head and neck.<ref>PMID:11801303</ref> Defects in PTEN are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[~~http~~://omim.org/entry/608089 608089]]. Note=PTEN mutations are found in a subset of patients with Proteus syndrome, a genetically heterogeneous condition. The molecular diagnosis of PTEN mutation positive cases classifies Proteus syndrome patients as part of the PTEN hamartoma syndrome spectrum. As such, patients surviving the early years of Proteus syndrome are likely at a greater risk of developing malignancies. Defects in PTEN are a cause of susceptibility to glioma type 2 (GLM2) [MIM:[~~http~~://omim.org/entry/613028 613028]]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Defects in PTEN are a cause of VACTERL association with hydrocephalus (VACTERL-H) [MIM:[~~http~~://omim.org/entry/276950 276950]]. VACTERL is an acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects. Defects in PTEN may be a cause of susceptibility to prostate cancer (PC) [MIM:[~~http~~://omim.org/entry/176807 176807]]. It is a malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Defects in PTEN are a cause of macrocephaly/autism syndrome (MCEPHAS) [MIM:[~~http~~://omim.org/entry/605309 605309]]. Patients have autism spectrum disorders and macrocephaly, with head circumferences ranging from +2.5 to +8 SD for age and sex (average head circumference +4.0 SD).<ref>PMID:15805158</ref> Note=A microdeletion of chromosome 10q23 involving BMPR1A and PTEN is a cause of chromosome 10q23 deletion syndrome, which shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome.		[https://www.uniprot.org/uniprot/PTEN_HUMAN PTEN_HUMAN] Defects in PTEN are a cause of Cowden disease (CD) [MIM:[https://omim.org/entry/158350 158350]; also known as Cowden syndrome (CS). CD is an autosomal dominant cancer predisposition syndrome associated with elevated risk for tumors of the breast, thyroid and skin. The predominant phenotype for CD is multiple hamartoma syndrome, in many organ systems including the breast (70% of CD patients), thyroid (40-60%), skin, CNS (40%), gastrointestinal tract. Affected individuals are at an increased risk of both breast and thyroid cancers. Trichilemmomas (benign tumors of the hair follicle infundibulum), and mucocutaneous papillomatosis (99%) are hallmarks of CD.<ref>PMID:9256433</ref> <ref>PMID:9811831</ref> <ref>PMID:9345101</ref> <ref>PMID:9399897</ref> <ref>PMID:9259288</ref> <ref>PMID:9140396</ref> <ref>PMID:9797362</ref> <ref>PMID:9600246</ref> <ref>PMID:9467011</ref> <ref>PMID:9735393</ref> <ref>PMID:9832031</ref> <ref>PMID:9425889</ref> <ref>PMID:9915974</ref> <ref>PMID:10051160</ref> <ref>PMID:10234502</ref> <ref>PMID:10866302</ref> <ref>PMID:11230179</ref> <ref>PMID:11494117</ref> Defects in PTEN are the cause of Lhermitte-Duclos disease (LDD) [MIM:[https://omim.org/entry/158350 158350]; also known as cerebelloparenchymal disorder VI. LDD is characterized by dysplastic gangliocytoma of the cerebellum which often results in cerebellar signs and seizures. LDD and CD seem to be the same entity, and are considered as hamartoma-neoplasia syndromes. Defects in PTEN are a cause of Bannayan-Zonana syndrome (BZS) [MIM:[https://omim.org/entry/153480 153480]; also known as Ruvalcaba-Myhre-Smith syndrome (RMSS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS). In BZS there seems not to be an increased risk of malignancy. It has a partial clinical overlap with CD. BZS is characterized by the classic triad of macrocephaly, lipomatosis and pigmented macules of the gland penis.<ref>PMID:9467011</ref> <ref>PMID:10866302</ref> <ref>PMID:11494117</ref> <ref>PMID:9241266</ref> <ref>PMID:10400993</ref> Defects in PTEN are a cause of head and neck squamous cell carcinomas (HNSCC) [MIM:[https://omim.org/entry/275355 275355]; also known as squamous cell carcinoma of the head and neck.<ref>PMID:11801303</ref> Defects in PTEN are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[https://omim.org/entry/608089 608089]. Note=PTEN mutations are found in a subset of patients with Proteus syndrome, a genetically heterogeneous condition. The molecular diagnosis of PTEN mutation positive cases classifies Proteus syndrome patients as part of the PTEN hamartoma syndrome spectrum. As such, patients surviving the early years of Proteus syndrome are likely at a greater risk of developing malignancies. Defects in PTEN are a cause of susceptibility to glioma type 2 (GLM2) [MIM:[https://omim.org/entry/613028 613028]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Defects in PTEN are a cause of VACTERL association with hydrocephalus (VACTERL-H) [MIM:[https://omim.org/entry/276950 276950]. VACTERL is an acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects. Defects in PTEN may be a cause of susceptibility to prostate cancer (PC) [MIM:[https://omim.org/entry/176807 176807]. It is a malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Defects in PTEN are a cause of macrocephaly/autism syndrome (MCEPHAS) [MIM:[https://omim.org/entry/605309 605309]. Patients have autism spectrum disorders and macrocephaly, with head circumferences ranging from +2.5 to +8 SD for age and sex (average head circumference +4.0 SD).<ref>PMID:15805158</ref> Note=A microdeletion of chromosome 10q23 involving BMPR1A and PTEN is a cause of chromosome 10q23 deletion syndrome, which shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome.
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/PTEN_HUMAN PTEN_HUMAN]] Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4. The lipid phosphatase activity is critical for its tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with AIP1 to suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability.<ref>PMID:9187108</ref> <ref>PMID:9256433</ref> <ref>PMID:9593664</ref> <ref>PMID:9811831</ref> <ref>PMID:9616126</ref> <ref>PMID:10468583</ref> <ref>PMID:11707428</ref> <ref>PMID:18716620</ref>		[https://www.uniprot.org/uniprot/PTEN_HUMAN PTEN_HUMAN] Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4. The lipid phosphatase activity is critical for its tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with AIP1 to suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability.<ref>PMID:9187108</ref> <ref>PMID:9256433</ref> <ref>PMID:9593664</ref> <ref>PMID:9811831</ref> <ref>PMID:9616126</ref> <ref>PMID:10468583</ref> <ref>PMID:11707428</ref> <ref>PMID:18716620</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 5bug" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5bug" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Dual specificity phosphatase 3D structures\|Dual specificity phosphatase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Bier, D]]		[[Category: Large Structures]]
	[[Category: Grossmann~~, T N~~]]		[[Category: Bier D]]
	[[Category: Hennig, S]]		[[Category: Grossmann TN]]
	[[Category: Lee, C U]]		[[Category: Hennig S]]
	~~[[Category: C2 domain]]~~		[[Category: Lee C-U]]
	~~[[Category: Disulfide]]~~
	~~[[Category: Hydrolase]]~~
	~~[[Category: Oxidized~~]]

OCA at 14:41, 16 November 2017

2017-11-16T14:41:53Z

← Older revision		Revision as of 14:41, 16 November 2017
Line 1:		Line 1:

	==Crystal structure of human phosphatase PTEN oxidized by H2O2==		==Crystal structure of human phosphatase PTEN oxidized by H2O2==
	<StructureSection load='5bug' size='340' side='right' caption='[[5bug]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='5bug' size='340' side='right' caption='[[5bug]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5bug]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BUG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BUG FirstGlance]. <br>		<table><tr><td colspan='2'>[[5bug]] is a 4 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=5BUG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BUG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5bug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bug OCA], [http://pdbe.org/5bug PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bug RCSB], [http://www.ebi.ac.uk/pdbsum/5bug PDBsum]</span></td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PTEN, MMAC1, TEP1 ([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=5bug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bug OCA], [http://pdbe.org/5bug PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bug RCSB], [http://www.ebi.ac.uk/pdbsum/5bug PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bug ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 23:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
	[[Category: Bier, D]]		[[Category: Bier, D]]
	[[Category: Grossmann, T N]]		[[Category: Grossmann, T N]]

OCA at 13:46, 7 October 2015

2015-10-07T13:46:37Z

← Older revision		Revision as of 13:46, 7 October 2015
Line 1:		Line 1:
	'''~~Unreleased~~ structure'''		==Crystal structure of human phosphatase PTEN oxidized by H2O2==
			<StructureSection load='5bug' size='340' side='right' caption='[[5bug]], [[Resolution\|resolution]] 2.40Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[5bug]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BUG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BUG FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr>
			<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5bug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bug OCA], [http://pdbe.org/5bug PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bug RCSB], [http://www.ebi.ac.uk/pdbsum/5bug PDBsum]</span></td></tr>
			</table>
			== Disease ==
			[[http://www.uniprot.org/uniprot/PTEN_HUMAN PTEN_HUMAN]] Defects in PTEN are a cause of Cowden disease (CD) [MIM:[http://omim.org/entry/158350 158350]]; also known as Cowden syndrome (CS). CD is an autosomal dominant cancer predisposition syndrome associated with elevated risk for tumors of the breast, thyroid and skin. The predominant phenotype for CD is multiple hamartoma syndrome, in many organ systems including the breast (70% of CD patients), thyroid (40-60%), skin, CNS (40%), gastrointestinal tract. Affected individuals are at an increased risk of both breast and thyroid cancers. Trichilemmomas (benign tumors of the hair follicle infundibulum), and mucocutaneous papillomatosis (99%) are hallmarks of CD.<ref>PMID:9256433</ref> <ref>PMID:9811831</ref> <ref>PMID:9345101</ref> <ref>PMID:9399897</ref> <ref>PMID:9259288</ref> <ref>PMID:9140396</ref> <ref>PMID:9797362</ref> <ref>PMID:9600246</ref> <ref>PMID:9467011</ref> <ref>PMID:9735393</ref> <ref>PMID:9832031</ref> <ref>PMID:9425889</ref> <ref>PMID:9915974</ref> <ref>PMID:10051160</ref> <ref>PMID:10234502</ref> <ref>PMID:10866302</ref> <ref>PMID:11230179</ref> <ref>PMID:11494117</ref> Defects in PTEN are the cause of Lhermitte-Duclos disease (LDD) [MIM:[http://omim.org/entry/158350 158350]]; also known as cerebelloparenchymal disorder VI. LDD is characterized by dysplastic gangliocytoma of the cerebellum which often results in cerebellar signs and seizures. LDD and CD seem to be the same entity, and are considered as hamartoma-neoplasia syndromes. Defects in PTEN are a cause of Bannayan-Zonana syndrome (BZS) [MIM:[http://omim.org/entry/153480 153480]]; also known as Ruvalcaba-Myhre-Smith syndrome (RMSS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS). In BZS there seems not to be an increased risk of malignancy. It has a partial clinical overlap with CD. BZS is characterized by the classic triad of macrocephaly, lipomatosis and pigmented macules of the gland penis.<ref>PMID:9467011</ref> <ref>PMID:10866302</ref> <ref>PMID:11494117</ref> <ref>PMID:9241266</ref> <ref>PMID:10400993</ref> Defects in PTEN are a cause of head and neck squamous cell carcinomas (HNSCC) [MIM:[http://omim.org/entry/275355 275355]]; also known as squamous cell carcinoma of the head and neck.<ref>PMID:11801303</ref> Defects in PTEN are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:[http://omim.org/entry/608089 608089]]. Note=PTEN mutations are found in a subset of patients with Proteus syndrome, a genetically heterogeneous condition. The molecular diagnosis of PTEN mutation positive cases classifies Proteus syndrome patients as part of the PTEN hamartoma syndrome spectrum. As such, patients surviving the early years of Proteus syndrome are likely at a greater risk of developing malignancies. Defects in PTEN are a cause of susceptibility to glioma type 2 (GLM2) [MIM:[http://omim.org/entry/613028 613028]]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Defects in PTEN are a cause of VACTERL association with hydrocephalus (VACTERL-H) [MIM:[http://omim.org/entry/276950 276950]]. VACTERL is an acronym for vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects. Defects in PTEN may be a cause of susceptibility to prostate cancer (PC) [MIM:[http://omim.org/entry/176807 176807]]. It is a malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Defects in PTEN are a cause of macrocephaly/autism syndrome (MCEPHAS) [MIM:[http://omim.org/entry/605309 605309]]. Patients have autism spectrum disorders and macrocephaly, with head circumferences ranging from +2.5 to +8 SD for age and sex (average head circumference +4.0 SD).<ref>PMID:15805158</ref> Note=A microdeletion of chromosome 10q23 involving BMPR1A and PTEN is a cause of chromosome 10q23 deletion syndrome, which shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome.
			== Function ==
			[[http://www.uniprot.org/uniprot/PTEN_HUMAN PTEN_HUMAN]] Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4. The lipid phosphatase activity is critical for its tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival. The unphosphorylated form cooperates with AIP1 to suppress AKT1 activation. Dephosphorylates tyrosine-phosphorylated focal adhesion kinase and inhibits cell migration and integrin-mediated cell spreading and focal adhesion formation. Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. May be a negative regulator of insulin signaling and glucose metabolism in adipose tissue. The nuclear monoubiquitinated form possesses greater apoptotic potential, whereas the cytoplasmic nonubiquitinated form induces less tumor suppressive ability.<ref>PMID:9187108</ref> <ref>PMID:9256433</ref> <ref>PMID:9593664</ref> <ref>PMID:9811831</ref> <ref>PMID:9616126</ref> <ref>PMID:10468583</ref> <ref>PMID:11707428</ref> <ref>PMID:18716620</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			PTEN is a dual-specificity protein tyrosine phosphatase. As one of the central tumor suppressors, a thorough regulation of its activity is essential for proper cellular homeostasis. The precise implications of PTEN inhibition by reactive oxygen species (e.g. H2 O2 ) and the subsequent structural consequences remain elusive. To study the effects of PTEN inhibition, bisperoxidovanadium (bpV) complexes serve as important tools with the potential for the treatment of nerve injury or cardiac ischemia. However, their mode of action is unknown, hampering further optimization and preventing therapeutic applications. Based on protein crystallography, mass spectrometry, and NMR spectroscopy, we elucidate the molecular basis of PTEN inhibition by H2 O2 and bpV complexes. We show that both molecules inhibit PTEN via oxidative mechanisms resulting in the formation of the same intramolecular disulfide, therefore enabling the reactivation of PTEN under reductive conditions.

	~~The entry 5bug is ON HOLD until Paper Publication~~		Redox Modulation of PTEN Phosphatase Activity by Hydrogen Peroxide and Bisperoxidovanadium Complexes.,Lee CU, Hahne G, Hanske J, Bange T, Bier D, Rademacher C, Hennig S, Grossmann TN Angew Chem Int Ed Engl. 2015 Sep 29. doi: 10.1002/anie.201506338. PMID:26418532<ref>PMID:26418532</ref>

	~~Authors: Lee~~, ~~C.-~~U.~~, Bier, D., Hennig,~~ S.~~, Grossmann, T.N~~.		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	~~Description~~: ~~Crystal structure of human phosphatase PTEN oxidized by H2O2~~		<div class="pdbe-citations 5bug" style="background-color:#fffaf0;"></div>
	~~[[Category: Unreleased Structures]]~~		== References ==
			<references/>
			__TOC__
			</StructureSection>
	[[Category: Bier, D]]		[[Category: Bier, D]]
	[[Category: ~~Lee~~, ~~C.-U~~]]		[[Category: Grossmann, T N]]
	[[Category: Hennig, S]]		[[Category: Hennig, S]]
	[[Category: ~~Grossmann~~, ~~T.N~~]]		[[Category: Lee, C U]]
			[[Category: C2 domain]]
			[[Category: Disulfide]]
			[[Category: Hydrolase]]
			[[Category: Oxidized]]

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OCA: Protected "5bug" [edit=sysop:move=sysop]

2015-06-10T13:04:50Z

Protected "5bug" [edit=sysop:move=sysop]

← Older revision	Revision as of 13:04, 10 June 2015
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OCA: New page: '''Unreleased structure''' The entry 5bug is ON HOLD Authors: Lee, C.-U., Bier, D., Hennig, S., Grossmann, T.N. Description: Crystal structure of human phosphatase PTEN oxidized by H2O...

2015-06-10T13:04:49Z

New page: '''Unreleased structure''' The entry 5bug is ON HOLD Authors: Lee, C.-U., Bier, D., Hennig, S., Grossmann, T.N. Description: Crystal structure of human phosphatase PTEN oxidized by H2O...

New page

'''Unreleased structure'''

The entry 5bug is ON HOLD

Authors: Lee, C.-U., Bier, D., Hennig, S., Grossmann, T.N.

Description: Crystal structure of human phosphatase PTEN oxidized by H2O2
[[Category: Unreleased Structures]]
[[Category: Bier, D]]
[[Category: Lee, C.-U]]
[[Category: Hennig, S]]
[[Category: Grossmann, T.N]]