1pty: Difference between revisions

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New page: left|200px<br /> <applet load="1pty" size="450" color="white" frame="true" align="right" spinBox="true" caption="1pty, resolution 1.85Å" /> '''CRYSTAL STRUCTURE O...
 
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[[Image:1pty.gif|left|200px]]<br />
<applet load="1pty" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1pty, resolution 1.85&Aring;" />
'''CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH TWO PHOSPHOTYROSINE MOLECULES'''<br />


==Overview==
==CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH TWO PHOSPHOTYROSINE MOLECULES==
The structure of the catalytically inactive mutant (C215S) of the human, protein-tyrosine phosphatase 1B (PTP1B) has been solved to high resolution, in two complexes. In the first, crystals were grown in the presence of, bis-(para-phosphophenyl) methane (BPPM), a synthetic high-affinity, low-molecular weight nonpeptidic substrate (Km = 16 microM), and the, structure was refined to an R-factor of 18. 2% at 1.9 A resolution. In the, second, crystals were grown in a saturating concentration of, phosphotyrosine (pTyr), and the structure was refined to an R-factor of, 18.1% at 1.85 A. Difference Fourier maps showed that BPPM binds PTP1B in, two mutually exclusive modes, one in which it occupies the canonical, pTyr-binding site (the active site), and another in which a phosphophenyl, moiety interacts with a set of residues not previously observed to bind, aryl phosphates. The identification of a second pTyr molecule at the same, site in the PTP1B/C215S-pTyr complex confirms that these residues, constitute a low-affinity noncatalytic aryl phosphate-binding site., Identification of a second aryl phosphate binding site adjacent to the, active site provides a paradigm for the design of tight-binding, highly, specific PTP1B inhibitors that can span both the active site and the, adjacent noncatalytic site. This design can be achieved by tethering, together two small ligands that are individually targeted to the active, site and the proximal noncatalytic site.
<StructureSection load='1pty' size='340' side='right'caption='[[1pty]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1pty]] 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=1PTY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PTY 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]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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=1pty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pty OCA], [https://pdbe.org/1pty PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pty RCSB], [https://www.ebi.ac.uk/pdbsum/1pty PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pty 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>
== 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/pt/1pty_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/main_output.php?pdb_ID=1pty ConSurf].
<div style="clear:both"></div>


==Disease==
==See Also==
Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176885 176885]], Insulin resistance, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176885 176885]]
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
 
== References ==
==About this Structure==
<references/>
1PTY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and PTR as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PTY OCA].
__TOC__
 
</StructureSection>
==Reference==
Identification of a second aryl phosphate-binding site in protein-tyrosine phosphatase 1B: a paradigm for inhibitor design., Puius YA, Zhao Y, Sullivan M, Lawrence DS, Almo SC, Zhang ZY, Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13420-5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9391040 9391040]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein-tyrosine-phosphatase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Almo SC]]
[[Category: Almo, S.C.]]
[[Category: Lawrence D]]
[[Category: Lawrence, D.]]
[[Category: Puius YA]]
[[Category: Puius, Y.A.]]
[[Category: Sullivan M]]
[[Category: Sullivan, M.]]
[[Category: Zhang Z-Y]]
[[Category: Zhang, Z.Y.]]
[[Category: Zhao Y]]
[[Category: Zhao, Y.]]
[[Category: MG]]
[[Category: PTR]]
[[Category: acetylation]]
[[Category: hydrolase]]
[[Category: inhibition]]
[[Category: peptide]]
[[Category: phosphorylation]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:47:09 2007''

Latest revision as of 12:00, 21 February 2024

CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH TWO PHOSPHOTYROSINE MOLECULESCRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH TWO PHOSPHOTYROSINE MOLECULES

Structural highlights

1pty is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.85Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Nievergall E, Janes PW, Stegmayer C, Vail ME, Haj FG, Teng SW, Neel BG, Bastiaens PI, Lackmann M. PTP1B regulates Eph receptor function and trafficking. J Cell Biol. 2010 Dec 13;191(6):1189-203. doi: 10.1083/jcb.201005035. Epub 2010, Dec 6. PMID:21135139 doi:10.1083/jcb.201005035
  2. ↑ Krishnan N, Fu C, Pappin DJ, Tonks NK. H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. Sci Signal. 2011 Dec 13;4(203):ra86. doi: 10.1126/scisignal.2002329. PMID:22169477 doi:10.1126/scisignal.2002329

1pty, resolution 1.85Å

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