OCA at 05:44, 5 July 2023

OCA — Wed, 05 Jul 2023 05:44:39 GMT

←Older revision		Revision as of 05:44, 5 July 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8f88 is ~~ON HOLD until 2024~~-11-21	+	==Crystal structure of PTP1B D181A/Q262A/C215A phosphatase domain with monophosphorylated JAK2 activation loop phosphopeptide==
		+	<StructureSection load='8f88' size='340' side='right'caption='[[8f88]], [[Resolution\|resolution]] 3.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8f88]] is a 6 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=8F88 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8F88 FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 3.1Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=8f88 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8f88 OCA], [https://pdbe.org/8f88 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8f88 RCSB], [https://www.ebi.ac.uk/pdbsum/8f88 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8f88 ProSAT]</span></td></tr>
		+	</table>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Protein Tyrosine Phosphatase 1B (PTP1B) is the prototypical protein tyrosine phosphatase and plays an essential role in the regulation of several kinase-driven signalling pathways. PTP1B displays a preference for bisphosphorylated substrates. Here we identify PTP1B as an inhibitor of IL-6 and show that, in vitro, it can dephosphorylate all four members of the JAK family. In order to gain a detailed understanding of the molecular mechanism of JAK dephosphorylation, we undertook a structural and biochemical analysis of the dephosphorylation reaction. We identified a product-trapping PTP1B mutant that allowed visualisation of the tyrosine and phosphate products of the reaction and a substrate-trapping mutant with a vastly decreased off-rate compared to those previously described. The latter mutant was used to determine the structure of bisphosphorylated JAK peptides bound to the enzyme active site. These structures revealed that the downstream phosphotyrosine preferentially engaged the active site, in contrast to the analogous region of IRK. Biochemical analysis confirmed this preference. In this binding mode, the previously identified second aryl binding site remains unoccupied and the non-substrate phosphotyrosine engages Arg47. Mutation of this arginine disrupts the preference for the downstream phosphotyrosine. This study reveals a previously unappreciated plasticity in how PTP1B interacts with different substrates.

-	~~Authors: Morris~~, R., Kershaw, N.J.~~, Babon, J~~.J.	+	Structure guided studies of the interaction between PTP1B and JAK.,Morris R, Keating N, Tan C, Chen H, Laktyushin A, Saiyed T, Liau NPD, Nicola NA, Tiganis T, Kershaw NJ, Babon JJ Commun Biol. 2023 Jun 14;6(1):641. doi: 10.1038/s42003-023-05020-9. PMID:37316570<ref>PMID:37316570</ref>

-	~~Description: Crystal structure~~ of ~~PTP1B D181A~~/~~Q262A~~/~~C215A phosphatase domain with monophosphorylated JAK2 activation loop phosphopeptide~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: Babon~~, J.J~~]]	+	<div class="pdbe-citations 8f88" style="background-color:#fffaf0;"></div>
-	[[Category: Kershaw~~, N.J~~]]	+	== References ==
-	[[Category: Morris, R]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Babon JJ]]
		+	[[Category: Kershaw NJ]]
		+	[[Category: Morris R]]

OCA at 05:46, 11 January 2023

OCA — Wed, 11 Jan 2023 05:46:32 GMT

←Older revision		Revision as of 05:46, 11 January 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8f88 is ON HOLD	+	The entry 8f88 is ON HOLD until 2024-11-21

	Authors: Morris, R., Kershaw, N.J., Babon, J.J.		Authors: Morris, R., Kershaw, N.J., Babon, J.J.

OCA: Protected "8f88" [edit=sysop:move=sysop]

OCA — Wed, 30 Nov 2022 08:40:49 GMT

Protected "8f88" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:40, 30 November 2022

OCA: New page: '''Unreleased structure''' The entry 8f88 is ON HOLD Authors: Morris, R., Kershaw, N.J., Babon, J.J. Description: Crystal structure of PTP1B D181A/Q262A/C215A phosphatase domain with m...

OCA — Wed, 30 Nov 2022 08:40:48 GMT

New page: '''Unreleased structure''' The entry 8f88 is ON HOLD Authors: Morris, R., Kershaw, N.J., Babon, J.J. Description: Crystal structure of PTP1B D181A/Q262A/C215A phosphatase domain with m...

New page

'''Unreleased structure'''

The entry 8f88 is ON HOLD

Authors: Morris, R., Kershaw, N.J., Babon, J.J.

Description: Crystal structure of PTP1B D181A/Q262A/C215A phosphatase domain with monophosphorylated JAK2 activation loop phosphopeptide
[[Category: Unreleased Structures]]
[[Category: Babon, J.J]]
[[Category: Kershaw, N.J]]
[[Category: Morris, R]]

8f88 - Revision history

OCA at 05:44, 5 July 2023

OCA at 05:46, 11 January 2023

OCA: Protected "8f88" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8f88 is ON HOLD Authors: Morris, R., Kershaw, N.J., Babon, J.J. Description: Crystal structure of PTP1B D181A/Q262A/C215A phosphatase domain with m...