7mn7: Difference between revisions
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==PTP1B F225Y in complex with TCS401== | ==PTP1B F225Y in complex with TCS401== | ||
<StructureSection load='7mn7' size='340' side='right'caption='[[7mn7]]' scene=''> | <StructureSection load='7mn7' size='340' side='right'caption='[[7mn7]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MN7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MN7 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7mn7]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MN7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MN7 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7mn7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mn7 OCA], [https://pdbe.org/7mn7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mn7 RCSB], [https://www.ebi.ac.uk/pdbsum/7mn7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mn7 ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=OTA:2-(OXALYL-AMINO)-4,5,6,7-TETRAHYDRO-THIENO[2,3-C]PYRIDINE-3-CARBOXYLIC+ACID'>OTA</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'>[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=7mn7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mn7 OCA], [https://pdbe.org/7mn7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mn7 RCSB], [https://www.ebi.ac.uk/pdbsum/7mn7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mn7 ProSAT]</span></td></tr> | |||
</table> | </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 == | |||
Homologous enzymes often exhibit different catalytic rates despite a fully conserved active site. The canonical view is that an enzyme sequence defines its structure and function and, more recently, that intrinsic protein dynamics at different time scales enable and/or promote catalytic activity. Here, we show that, using the protein tyrosine phosphatase PTP1B, residues surrounding the PTP1B active site promote dynamically coordinated chemistry necessary for PTP1B function. However, residues distant to the active site also undergo distinct intermediate time scale dynamics and these dynamics are correlated with its catalytic activity and thus allow for different catalytic rates in this enzyme family. We identify these previously undetected motions using coevolutionary coupling analysis and nuclear magnetic resonance spectroscopy. Our findings strongly indicate that conserved dynamics drives the enzymatic activity of the PTP family. Characterization of these conserved dynamics allows for the identification of novel regulatory elements (therapeutic binding pockets) that can be leveraged for the control of enzymes. | |||
Conserved conformational dynamics determine enzyme activity.,Torgeson KR, Clarkson MW, Granata D, Lindorff-Larsen K, Page R, Peti W Sci Adv. 2022 Aug 5;8(31):eabo5546. doi: 10.1126/sciadv.abo5546. Epub 2022 Aug 3. PMID:35921420<ref>PMID:35921420</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7mn7" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Page R]] | [[Category: Protein-tyrosine-phosphatase]] | ||
[[Category: Peti W]] | [[Category: Page, R]] | ||
[[Category: Torgeson | [[Category: Peti, W]] | ||
[[Category: Torgeson, K R]] | |||
[[Category: Hydrolase]] | |||
[[Category: Protein tyrosine phosphatase]] | |||
Revision as of 08:10, 25 August 2022
PTP1B F225Y in complex with TCS401PTP1B F225Y in complex with TCS401
Structural highlights
Function[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.[1] [2] Publication Abstract from PubMedHomologous enzymes often exhibit different catalytic rates despite a fully conserved active site. The canonical view is that an enzyme sequence defines its structure and function and, more recently, that intrinsic protein dynamics at different time scales enable and/or promote catalytic activity. Here, we show that, using the protein tyrosine phosphatase PTP1B, residues surrounding the PTP1B active site promote dynamically coordinated chemistry necessary for PTP1B function. However, residues distant to the active site also undergo distinct intermediate time scale dynamics and these dynamics are correlated with its catalytic activity and thus allow for different catalytic rates in this enzyme family. We identify these previously undetected motions using coevolutionary coupling analysis and nuclear magnetic resonance spectroscopy. Our findings strongly indicate that conserved dynamics drives the enzymatic activity of the PTP family. Characterization of these conserved dynamics allows for the identification of novel regulatory elements (therapeutic binding pockets) that can be leveraged for the control of enzymes. Conserved conformational dynamics determine enzyme activity.,Torgeson KR, Clarkson MW, Granata D, Lindorff-Larsen K, Page R, Peti W Sci Adv. 2022 Aug 5;8(31):eabo5546. doi: 10.1126/sciadv.abo5546. Epub 2022 Aug 3. PMID:35921420[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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