6b95: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Multiconformer model of K197C PTP1B tethered to compound 2 at 100 K== | ==Multiconformer model of K197C PTP1B tethered to compound 2 at 100 K== | ||
<StructureSection load='6b95' size='340' side='right' caption='[[6b95]], [[Resolution|resolution]] 1.95Å' scene=''> | <StructureSection load='6b95' size='340' side='right'caption='[[6b95]], [[Resolution|resolution]] 1.95Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6b95]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6b95]] 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=6B95 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B95 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D0P:N-(2,4-difluoro-4-hydroxy[1,1-biphenyl]-3-yl)-2-sulfanylacetamide'>D0P</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=D0P:N-(2,4-difluoro-4-hydroxy[1,1-biphenyl]-3-yl)-2-sulfanylacetamide'>D0P</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6b90|6b90]], [[6b8e|6b8e]], [[6b8t|6b8t]], [[6b8x|6b8x]], [[6b8z|6b8z]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6b90|6b90]], [[6b8e|6b8e]], [[6b8t|6b8t]], [[6b8x|6b8x]], [[6b8z|6b8z]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPN1, PTP1B ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPN1, PTP1B ([https://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'>[ | <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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6b95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b95 OCA], [https://pdbe.org/6b95 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b95 RCSB], [https://www.ebi.ac.uk/pdbsum/6b95 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b95 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> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 23: | ||
==See Also== | ==See Also== | ||
*[[Tyrosine phosphatase|Tyrosine phosphatase]] | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 29: | Line 29: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Protein-tyrosine-phosphatase]] | [[Category: Protein-tyrosine-phosphatase]] | ||
[[Category: Biel, J T]] | [[Category: Biel, J T]] | ||
Revision as of 14:38, 23 March 2022
Multiconformer model of K197C PTP1B tethered to compound 2 at 100 KMulticonformer model of K197C PTP1B tethered to compound 2 at 100 K
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 PubMedAllostery 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||||
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCACategories:
- Human
- Large Structures
- Protein-tyrosine-phosphatase
- Biel, J T
- Brandao-Neto, J
- Delft, F von
- Fraser, J S
- Hill, Z B
- Kang, E
- Keedy, D A
- Rettenmaier, T J
- Wells, J A
- Allostery
- Covalent ligand
- Enzyme
- Multiconformer
- Multitemperature
- Protein tyrosine phosphatase
- Protein tyrosine phosphatase 1b
- Ptp
- Ptp1b
- Signaling protein
- Tethering