1l8g - Revision history

OCA at 07:30, 14 February 2024

OCA — Wed, 14 Feb 2024 07:30:43 GMT

←Older revision		Revision as of 07:30, 14 February 2024
Line 3:		Line 3:
	<StructureSection load='1l8g' size='340' side='right'caption='[[1l8g]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1l8g' size='340' side='right'caption='[[1l8g]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1l8g]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L8G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L8G FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1l8g]] 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=1L8G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L8G FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=DBD:7~~-(1,~~1-DIOXO-1H-BENZO~~[D]~~ISOTHIAZOL-3-YLOXYMETHYL)-~~2~~-(OXALYL-AMINO)-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC+ACID'>DBD</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]] 2.5Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style='overflow: auto; max-height: 3em;'>[[1c83\|1c83]]</div></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DBD:7-(1,1-DIOXO-1H-BENZO[D]ISOTHIAZOL-3-YLOXYMETHYL)-2-(OXALYL-AMINO)-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC+ACID'>DBD</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=1l8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8g OCA], [https://pdbe.org/1l8g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l8g RCSB], [https://www.ebi.ac.uk/pdbsum/1l8g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l8g 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=1l8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8g OCA], [https://pdbe.org/1l8g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l8g RCSB], [https://www.ebi.ac.uk/pdbsum/1l8g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l8g ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/PTN1_HUMAN PTN1_HUMAN]] Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.<ref>PMID:21135139</ref> <ref>PMID:22169477</ref>	+	[https://www.uniprot.org/uniprot/PTN1_HUMAN PTN1_HUMAN] Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.<ref>PMID:21135139</ref> <ref>PMID:22169477</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</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=1l8g 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=1l8g ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Utilizing structure-based design, we have previously demonstrated that it is possible to obtain selective inhibitors of protein-tyrosine phosphatase 1B (PTP1B). A basic nitrogen was introduced into a general PTP inhibitor to form a salt bridge to Asp48 in PTP1B and simultaneously cause repulsion in PTPs containing an asparagine in the equivalent position [Iversen, L. F., et al. (2000) J. Biol. Chem. 275, 10300-10307]. Further, we have recently demonstrated that Gly259 in PTP1B forms the bottom of a gateway that allows easy access to the active site for a broad range of substrates, while bulky residues in the same position in other PTPs cause steric hindrance and reduced substrate recognition capacity [Peters, G. H., et al. (2000) J. Biol. Chem. 275, 18201-18209]. The current study was undertaken to investigate the feasibility of structure-based design, utilizing these differences in accessibility to the active site among various PTPs. We show that a general, low-molecular weight PTP inhibitor can be developed into a highly selective inhibitor for PTP1B and TC-PTP by introducing a substituent, which is designed to address the region around residues 258 and 259. Detailed enzyme kinetic analysis with a set of wild-type and mutant PTPs, X-ray protein crystallography, and molecular modeling studies confirmed that selectivity for PTP1B and TC-PTP was achieved due to steric hindrance imposed by bulky position 259 residues in other PTPs.
-
-	Steric hindrance as a basis for structure-based design of selective inhibitors of protein-tyrosine phosphatases.,Iversen LF, Andersen HS, Moller KB, Olsen OH, Peters GH, Branner S, Mortensen SB, Hansen TK, Lau J, Ge Y, Holsworth DD, Newman MJ, Hundahl Moller NP Biochemistry. 2001 Dec 11;40(49):14812-20. PMID:11732900<ref>PMID:11732900</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1l8g" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Protein-tyrosine-phosphatase]]~~	+	[[Category: Andersen HS]]
-	[[Category: Andersen~~, H S~~]]	+	[[Category: Branner S]]
-	[[Category: Branner, S]]	+	[[Category: Ge Y]]
-	[[Category: Ge, Y]]	+	[[Category: Hansen TK]]
-	[[Category: Hansen~~, T K~~]]	+	[[Category: Holsworth DD]]
-	[[Category: Holsworth~~, D D~~]]	+	[[Category: Iversen LF]]
-	[[Category: Iversen~~, L F~~]]	+	[[Category: Lau J]]
-	[[Category: Lau, J]]	+	[[Category: Moller KB]]
-	[[Category: Moller~~, K B~~]]	+	[[Category: Moller NPH]]
-	[[Category: Moller~~, N P.H~~]]	+	[[Category: Mortensen SB]]
-	[[Category: Mortensen~~, S B~~]]	+	[[Category: Newman MJ]]
-	[[Category: Newman~~, M J~~]]	+	[[Category: Olsen OH]]
-	[[Category: Olsen~~, O H~~]]	+	[[Category: Peters GH]]
-	[[Category: Peters~~, G H]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Protein-inhibitor~~]]	+

OCA at 06:41, 18 August 2021

OCA — Wed, 18 Aug 2021 06:41:20 GMT

←Older revision		Revision as of 06:41, 18 August 2021
Line 3:		Line 3:
	<StructureSection load='1l8g' size='340' side='right'caption='[[1l8g]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1l8g' size='340' side='right'caption='[[1l8g]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1l8g]] 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=1L8G OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1L8G FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1l8g]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L8G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L8G FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DBD:7-(1,1-DIOXO-1H-BENZO[D]ISOTHIAZOL-3-YLOXYMETHYL)-2-(OXALYL-AMINO)-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC+ACID'>DBD</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DBD:7-(1,1-DIOXO-1H-BENZO[D]ISOTHIAZOL-3-YLOXYMETHYL)-2-(OXALYL-AMINO)-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC+ACID'>DBD</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1c83\|1c83]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1c83\|1c83]]</div></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'>[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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1l8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8g OCA], [~~http~~://pdbe.org/1l8g PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1l8g RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1l8g PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1l8g 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=1l8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8g OCA], [https://pdbe.org/1l8g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l8g RCSB], [https://www.ebi.ac.uk/pdbsum/1l8g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l8g ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/PTN1_HUMAN PTN1_HUMAN]] Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.<ref>PMID:21135139</ref> <ref>PMID:22169477</ref>	+	[[https://www.uniprot.org/uniprot/PTN1_HUMAN PTN1_HUMAN]] Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.<ref>PMID:21135139</ref> <ref>PMID:22169477</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	==See Also==		==See Also==
-	*[[Tyrosine phosphatase\|Tyrosine phosphatase]]	+	*[[Tyrosine phosphatase 3D structures\|Tyrosine phosphatase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:11, 13 November 2019

OCA — Wed, 13 Nov 2019 12:11:34 GMT

←Older revision		Revision as of 12:11, 13 November 2019
Line 1:		Line 1:

	==Crystal structure of PTP1B complexed with 7-(1,1-Dioxo-1H-benzo[d]isothiazol-3-yloxymethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid==		==Crystal structure of PTP1B complexed with 7-(1,1-Dioxo-1H-benzo[d]isothiazol-3-yloxymethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid==
-	<StructureSection load='1l8g' size='340' side='right' caption='[[1l8g]], [[Resolution\|resolution]] 2.50Å' scene=''>	+	<StructureSection load='1l8g' size='340' side='right'caption='[[1l8g]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1l8g]] 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=1L8G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1L8G FirstGlance]. <br>		<table><tr><td colspan='2'>[[1l8g]] 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=1L8G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1L8G FirstGlance]. <br>
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	</div>		</div>
	<div class="pdbe-citations 1l8g" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1l8g" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Tyrosine phosphatase\|Tyrosine phosphatase]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Protein-tyrosine-phosphatase]]		[[Category: Protein-tyrosine-phosphatase]]
	[[Category: Andersen, H S]]		[[Category: Andersen, H S]]

OCA at 21:21, 24 January 2018

OCA — Wed, 24 Jan 2018 21:21:03 GMT

←Older revision		Revision as of 21:21, 24 January 2018
Line 1:		Line 1:
		+
	==Crystal structure of PTP1B complexed with 7-(1,1-Dioxo-1H-benzo[d]isothiazol-3-yloxymethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid==		==Crystal structure of PTP1B complexed with 7-(1,1-Dioxo-1H-benzo[d]isothiazol-3-yloxymethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid==
	<StructureSection load='1l8g' size='340' side='right' caption='[[1l8g]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1l8g' size='340' side='right' caption='[[1l8g]], [[Resolution\|resolution]] 2.50Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1c83\|1c83]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1c83\|1c83]]</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=1l8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8g OCA], [http://pdbe.org/1l8g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1l8g RCSB], [http://www.ebi.ac.uk/pdbsum/1l8g 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=1l8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8g OCA], [http://pdbe.org/1l8g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1l8g RCSB], [http://www.ebi.ac.uk/pdbsum/1l8g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1l8g ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 14:		Line 15:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l8/1l8g_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l8/1l8g_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 29:		Line 30:
	</div>		</div>
	<div class="pdbe-citations 1l8g" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1l8g" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Tyrosine phosphatase\|Tyrosine phosphatase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 02:11, 7 February 2016

OCA — Sun, 07 Feb 2016 02:11:51 GMT

←Older revision		Revision as of 02:11, 7 February 2016
Line 18:		Line 18:
	<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=1l8g ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 20:41, 9 September 2015

OCA — Wed, 09 Sep 2015 20:41:12 GMT

←Older revision		Revision as of 20:41, 9 September 2015
Line 2:		Line 2:
	<StructureSection load='1l8g' size='340' side='right' caption='[[1l8g]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='1l8g' size='340' side='right' caption='[[1l8g]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1l8g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L8G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1L8G FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1l8g]] 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=1L8G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1L8G FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DBD:7-(1,1-DIOXO-1H-BENZO[D]ISOTHIAZOL-3-YLOXYMETHYL)-2-(OXALYL-AMINO)-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC+ACID'>DBD</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DBD:7-(1,1-DIOXO-1H-BENZO[D]ISOTHIAZOL-3-YLOXYMETHYL)-2-(OXALYL-AMINO)-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC+ACID'>DBD</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1c83\|1c83]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1c83\|1c83]]</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=1l8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1l8g RCSB], [http://www.ebi.ac.uk/pdbsum/1l8g 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=1l8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8g OCA], [http://pdbe.org/1l8g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1l8g RCSB], [http://www.ebi.ac.uk/pdbsum/1l8g PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 28:		Line 28:
	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 1l8g" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 35:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Protein-tyrosine-phosphatase]]		[[Category: Protein-tyrosine-phosphatase]]
	[[Category: Andersen, H S]]		[[Category: Andersen, H S]]

OCA at 06:58, 24 December 2014

OCA — Wed, 24 Dec 2014 06:58:23 GMT

←Older revision		Revision as of 06:58, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1l8g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L8G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1L8G FirstGlance]. <br>		<table><tr><td colspan='2'>[[1l8g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L8G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1L8G FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DBD:7-(1,1-DIOXO-1H-BENZO[D]ISOTHIAZOL-3-YLOXYMETHYL)-2-(OXALYL-AMINO)-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC+ACID'>DBD</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DBD:7-(1,1-DIOXO-1H-BENZO[D]ISOTHIAZOL-3-YLOXYMETHYL)-2-(OXALYL-AMINO)-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC+ACID'>DBD</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1c83\|1c83]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1c83\|1c83]]</td></tr>
-	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1l8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1l8g RCSB], [http://www.ebi.ac.uk/pdbsum/1l8g 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=1l8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1l8g RCSB], [http://www.ebi.ac.uk/pdbsum/1l8g PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PTN1_HUMAN PTN1_HUMAN]] Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.<ref>PMID:21135139</ref> <ref>PMID:22169477</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 35:		Line 37:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Protein-tyrosine-phosphatase]]		[[Category: Protein-tyrosine-phosphatase]]
-	[[Category: Andersen, H S.]]	+	[[Category: Andersen, H S]]
-	[[Category: Branner, S.]]	+	[[Category: Branner, S]]
-	[[Category: Ge, Y.]]	+	[[Category: Ge, Y]]
-	[[Category: Hansen, T K.]]	+	[[Category: Hansen, T K]]
-	[[Category: Holsworth, D D.]]	+	[[Category: Holsworth, D D]]
-	[[Category: Iversen, L F.]]	+	[[Category: Iversen, L F]]
-	[[Category: Lau, J.]]	+	[[Category: Lau, J]]
-	[[Category: Moller, K B.]]	+	[[Category: Moller, K B]]
-	[[Category: Moller, N P.H.]]	+	[[Category: Moller, N P.H]]
-	[[Category: Mortensen, S B.]]	+	[[Category: Mortensen, S B]]
-	[[Category: Newman, M J.]]	+	[[Category: Newman, M J]]
-	[[Category: Olsen, O H.]]	+	[[Category: Olsen, O H]]
-	[[Category: Peters, G H.]]	+	[[Category: Peters, G H]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Protein-inhibitor]]		[[Category: Protein-inhibitor]]

OCA at 13:09, 28 September 2014

OCA — Sun, 28 Sep 2014 13:09:52 GMT

←Older revision		Revision as of 13:09, 28 September 2014
Line 1:		Line 1:
-	[[~~Image:~~1l8g.~~png~~\|~~left~~\|200px]]	+	==Crystal structure of PTP1B complexed with 7-(1,1-Dioxo-1H-benzo[d]isothiazol-3-yloxymethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid==
		+	<StructureSection load='1l8g' size='340' side='right' caption='[[1l8g]], [[Resolution\|resolution]] 2.50Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1l8g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L8G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1L8G FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DBD:7-(1,1-DIOXO-1H-BENZO[D]ISOTHIAZOL-3-YLOXYMETHYL)-2-(OXALYL-AMINO)-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC+ACID'>DBD</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1c83\|1c83]]</td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1l8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1l8g RCSB], [http://www.ebi.ac.uk/pdbsum/1l8g 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/l8/1l8g_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 ==
		+	Utilizing structure-based design, we have previously demonstrated that it is possible to obtain selective inhibitors of protein-tyrosine phosphatase 1B (PTP1B). A basic nitrogen was introduced into a general PTP inhibitor to form a salt bridge to Asp48 in PTP1B and simultaneously cause repulsion in PTPs containing an asparagine in the equivalent position [Iversen, L. F., et al. (2000) J. Biol. Chem. 275, 10300-10307]. Further, we have recently demonstrated that Gly259 in PTP1B forms the bottom of a gateway that allows easy access to the active site for a broad range of substrates, while bulky residues in the same position in other PTPs cause steric hindrance and reduced substrate recognition capacity [Peters, G. H., et al. (2000) J. Biol. Chem. 275, 18201-18209]. The current study was undertaken to investigate the feasibility of structure-based design, utilizing these differences in accessibility to the active site among various PTPs. We show that a general, low-molecular weight PTP inhibitor can be developed into a highly selective inhibitor for PTP1B and TC-PTP by introducing a substituent, which is designed to address the region around residues 258 and 259. Detailed enzyme kinetic analysis with a set of wild-type and mutant PTPs, X-ray protein crystallography, and molecular modeling studies confirmed that selectivity for PTP1B and TC-PTP was achieved due to steric hindrance imposed by bulky position 259 residues in other PTPs.

-	~~{{STRUCTURE_1l8g\| PDB=1l8g \| SCENE= }}~~	+	Steric hindrance as a basis for structure-based design of selective inhibitors of protein-tyrosine phosphatases.,Iversen LF, Andersen HS, Moller KB, Olsen OH, Peters GH, Branner S, Mortensen SB, Hansen TK, Lau J, Ge Y, Holsworth DD, Newman MJ, Hundahl Moller NP Biochemistry. 2001 Dec 11;40(49):14812-20. PMID:11732900<ref>PMID:11732900</ref>

-	~~===Crystal structure of PTP1B complexed with 7-(1~~,~~1-Dioxo-1H-benzo[d]isothiazol-3-yloxymethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_11732900}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[1l8g]] is~~ a ~~1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=1L8G OCA].~~	+

	==See Also==		==See Also==
	*[[Tyrosine phosphatase\|Tyrosine phosphatase]]		*[[Tyrosine phosphatase\|Tyrosine phosphatase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:011732900<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Protein-tyrosine-phosphatase]]		[[Category: Protein-tyrosine-phosphatase]]

OCA at 05:18, 20 October 2012

OCA — Sat, 20 Oct 2012 05:18:41 GMT

←Older revision		Revision as of 05:18, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1l8g]] is a 1 chain structure ~~of [[Tyrosine phosphatase]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L8G OCA].	+	[[1l8g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L8G OCA].

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

OCA at 11:35, 14 August 2012

OCA — Tue, 14 Aug 2012 11:35:14 GMT

←Older revision		Revision as of 11:35, 14 August 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1l8g]] is a 1 chain structure of ~~[[Proten tyrosine phosphatase]] and~~ [[Tyrosine phosphatase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L8G OCA].	+	[[1l8g]] is a 1 chain structure of [[Tyrosine phosphatase]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L8G OCA].

	==See Also==		==See Also==
-	*[[Proten tyrosine phosphatase\|Proten tyrosine phosphatase]]
	*[[Tyrosine phosphatase\|Tyrosine phosphatase]]		*[[Tyrosine phosphatase\|Tyrosine phosphatase]]