5qe2 - Revision history

OCA at 08:52, 7 February 2024

OCA — Wed, 07 Feb 2024 08:52:34 GMT

←Older revision		Revision as of 08:52, 7 February 2024
Line 3:		Line 3:
	<StructureSection load='5qe2' size='340' side='right'caption='[[5qe2]], [[Resolution\|resolution]] 1.79Å' scene=''>		<StructureSection load='5qe2' size='340' side='right'caption='[[5qe2]], [[Resolution\|resolution]] 1.79Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5qe2]] 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=5QE2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5QE2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5qe2]] 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=5QE2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5QE2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JGY:1-methyl-N-{[(2S)-oxolan-2-yl]methyl}-1H-pyrazole-3-carboxamide'>JGY</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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]] 1.787Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PTPN1, PTP1B ([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=JGY:1-methyl-N-{[(2S)-oxolan-2-yl]methyl}-1H-pyrazole-3-carboxamide'>JGY</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=5qe2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qe2 OCA], [https://pdbe.org/5qe2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5qe2 RCSB], [https://www.ebi.ac.uk/pdbsum/5qe2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5qe2 ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5qe2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qe2 OCA], [~~http~~://pdbe.org/5qe2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5qe2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5qe2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5qe2 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>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Allostery is an inherent feature of proteins, but it remains challenging to reveal the mechanisms by which allosteric signals propagate. A clearer understanding of this intrinsic circuitry would afford new opportunities to modulate protein function. Here we have identified allosteric sites in protein tyrosine phosphatase 1B (PTP1B) by combining multiple-temperature X-ray crystallography experiments and structure determination from hundreds of individual small-molecule fragment soaks. New modeling approaches reveal 'hidden' low-occupancy conformational states for protein and ligands. Our results converge on allosteric sites that are conformationally coupled to the active-site WPD loop and are hotspots for fragment binding. Targeting one of these sites with covalently tethered molecules or mutations allosterically inhibits enzyme activity. Overall, this work demonstrates how the ensemble nature of macromolecular structure, revealed here by multitemperature crystallography, can elucidate allosteric mechanisms and open new doors for long-range control of protein function.	+
-		+
-	An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering.,Keedy DA, Hill ZB, Biel JT, Kang E, Rettenmaier TJ, Brandao-Neto J, Pearce NM, von Delft F, Wells JA, Fraser JS Elife. 2018 Jun 7;7. pii: 36307. doi: 10.7554/eLife.36307. PMID:29877794<ref>PMID:29877794</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5qe2" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 27:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Protein-tyrosine-phosphatase]]~~	+	[[Category: Biel JT]]
-	[[Category: Biel~~, J T~~]]	+	[[Category: Brandao-Neto J]]
-	[[Category: Brandao-Neto, J]]	+	[[Category: Fraser JS]]
-	~~[[Category: Delft, F von~~]]	+	[[Category: Hill ZB]]
-	[[Category: Fraser~~, J S~~]]	+	[[Category: Kang E]]
-	[[Category: Hill~~, Z B~~]]	+	[[Category: Keedy DA]]
-	[[Category: Kang, E]]	+	[[Category: Rettenmaier TJ]]
-	[[Category: Keedy~~, D A~~]]	+	[[Category: Wells JA]]
-	[[Category: Rettenmaier~~, T J~~]]	+	[[Category: Von Delft F]]
-	[[Category: Wells~~, J A~~]]	+
-	[[Category: ~~Allostery]]~~	+
-	~~[[Category: Enzyme]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Multiconformer]]~~	+
-	~~[[Category: Pandda]]~~	+
-	~~[[Category: Protein tyrosine phosphatase]]~~	+
-	~~[[Category: Protein tyrosine phosphatase 1b]]~~	+
-	~~[[Category: Ptp]]~~	+
-	~~[[Category: Ptp1b]]~~	+
-	~~[[Category: Sgc - diamond i04-1 fragment screening~~]]	+

OCA at 11:01, 16 September 2020

OCA — Wed, 16 Sep 2020 11:01:17 GMT

←Older revision		Revision as of 11:01, 16 September 2020
Line 1:		Line 1:

	==PanDDA analysis group deposition -- Crystal structure of PTP1B in complex with compound_FMOPL000398a==		==PanDDA analysis group deposition -- Crystal structure of PTP1B in complex with compound_FMOPL000398a==
-	<StructureSection load='5qe2' size='340' side='right' caption='[[5qe2]], [[Resolution\|resolution]] 1.79Å' scene=''>	+	<StructureSection load='5qe2' size='340' side='right'caption='[[5qe2]], [[Resolution\|resolution]] 1.79Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5qe2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5QE2 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5QE2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5qe2]] 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=5QE2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5QE2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JGY:1-methyl-N-{[(2S)-oxolan-2-yl]methyl}-1H-pyrazole-3-carboxamide'>JGY</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JGY:1-methyl-N-{[(2S)-oxolan-2-yl]methyl}-1H-pyrazole-3-carboxamide'>JGY</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PTPN1, PTP1B ([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=5qe2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qe2 OCA], [http://pdbe.org/5qe2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5qe2 RCSB], [http://www.ebi.ac.uk/pdbsum/5qe2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5qe2 ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5qe2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qe2 OCA], [http://pdbe.org/5qe2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5qe2 RCSB], [http://www.ebi.ac.uk/pdbsum/5qe2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5qe2 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>		[[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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Allostery is an inherent feature of proteins, but it remains challenging to reveal the mechanisms by which allosteric signals propagate. A clearer understanding of this intrinsic circuitry would afford new opportunities to modulate protein function. Here we have identified allosteric sites in protein tyrosine phosphatase 1B (PTP1B) by combining multiple-temperature X-ray crystallography experiments and structure determination from hundreds of individual small-molecule fragment soaks. New modeling approaches reveal 'hidden' low-occupancy conformational states for protein and ligands. Our results converge on allosteric sites that are conformationally coupled to the active-site WPD loop and are hotspots for fragment binding. Targeting one of these sites with covalently tethered molecules or mutations allosterically inhibits enzyme activity. Overall, this work demonstrates how the ensemble nature of macromolecular structure, revealed here by multitemperature crystallography, can elucidate allosteric mechanisms and open new doors for long-range control of protein function.
		+
		+	An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering.,Keedy DA, Hill ZB, Biel JT, Kang E, Rettenmaier TJ, Brandao-Neto J, Pearce NM, von Delft F, Wells JA, Fraser JS Elife. 2018 Jun 7;7. pii: 36307. doi: 10.7554/eLife.36307. PMID:29877794<ref>PMID:29877794</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5qe2" 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: Large Structures]]
	[[Category: Protein-tyrosine-phosphatase]]		[[Category: Protein-tyrosine-phosphatase]]
	[[Category: Biel, J T]]		[[Category: Biel, J T]]

OCA at 07:50, 10 October 2018

OCA — Wed, 10 Oct 2018 07:50:02 GMT

←Older revision		Revision as of 07:50, 10 October 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5qe2 ~~is ON HOLD~~	+	==PanDDA analysis group deposition -- Crystal structure of PTP1B in complex with compound_FMOPL000398a==
-		+	<StructureSection load='5qe2' size='340' side='right' caption='[[5qe2]], [[Resolution\|resolution]] 1.79Å' scene=''>
-	~~Authors~~: ~~Keedy, D~~.A.~~, Hill, Z~~.B.~~, Biel, J~~.T., ~~Kang~~, E., ~~Rettenmaier, T~~.J.~~, Brandao~~-~~Neto~~, J., ~~von Delft~~, F., ~~Wells, J~~.A., ~~Fraser, J~~.S.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5qe2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5QE2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5QE2 FirstGlance]. <br>
-	~~Description: PanDDA analysis group deposition --Crystal structure of PTP1B in complex with compound_FMOPL000398a~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=JGY:1-methyl-N-{[(2S)-oxolan-2-yl]methyl}-1H-pyrazole-3-carboxamide'>JGY</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<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>
-	[[Category: ~~Biel, J.T~~]]	+	<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=5qe2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5qe2 OCA], [http://pdbe.org/5qe2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5qe2 RCSB], [http://www.ebi.ac.uk/pdbsum/5qe2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5qe2 ProSAT]</span></td></tr>
-	[[Category: ~~Rettenmaier~~, T.J]]	+	</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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Protein-tyrosine-phosphatase]]
		+	[[Category: Biel, J T]]
	[[Category: Brandao-Neto, J]]		[[Category: Brandao-Neto, J]]
-	[[Category: ~~Keedy~~, ~~D.A~~]]	+	[[Category: Delft, F von]]
-	[[Category: ~~Wells~~, J.A]]	+	[[Category: Fraser, J S]]
-	[[Category: Hill, Z.B]]	+	[[Category: Hill, Z B]]
-	~~[[Category: Fraser, J.S~~]]	+
	[[Category: Kang, E]]		[[Category: Kang, E]]
-	[[Category: ~~Von Delft~~, F]]	+	[[Category: Keedy, D A]]
		+	[[Category: Rettenmaier, T J]]
		+	[[Category: Wells, J A]]
		+	[[Category: Allostery]]
		+	[[Category: Enzyme]]
		+	[[Category: Hydrolase]]
		+	[[Category: Multiconformer]]
		+	[[Category: Pandda]]
		+	[[Category: Protein tyrosine phosphatase]]
		+	[[Category: Protein tyrosine phosphatase 1b]]
		+	[[Category: Ptp]]
		+	[[Category: Ptp1b]]
		+	[[Category: Sgc - diamond i04-1 fragment screening]]

OCA: Protected "5qe2" [edit=sysop:move=sysop]

OCA — Wed, 28 Feb 2018 04:46:56 GMT

Protected "5qe2" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:46, 28 February 2018

OCA: New page: '''Unreleased structure''' The entry 5qe2 is ON HOLD Authors: Keedy, D.A., Hill, Z.B., Biel, J.T., Kang, E., Rettenmaier, T.J., Brandao-Neto, J., von Delft, F., Wells, J.A., Fraser, J.S...

OCA — Wed, 28 Feb 2018 04:46:54 GMT

New page: '''Unreleased structure''' The entry 5qe2 is ON HOLD Authors: Keedy, D.A., Hill, Z.B., Biel, J.T., Kang, E., Rettenmaier, T.J., Brandao-Neto, J., von Delft, F., Wells, J.A., Fraser, J.S...

New page

'''Unreleased structure'''

The entry 5qe2 is ON HOLD

Authors: Keedy, D.A., Hill, Z.B., Biel, J.T., Kang, E., Rettenmaier, T.J., Brandao-Neto, J., von Delft, F., Wells, J.A., Fraser, J.S.

Description: PanDDA analysis group deposition --Crystal structure of PTP1B in complex with compound_FMOPL000398a
[[Category: Unreleased Structures]]
[[Category: Biel, J.T]]
[[Category: Rettenmaier, T.J]]
[[Category: Brandao-Neto, J]]
[[Category: Keedy, D.A]]
[[Category: Wells, J.A]]
[[Category: Hill, Z.B]]
[[Category: Fraser, J.S]]
[[Category: Kang, E]]
[[Category: Von Delft, F]]