1pty: Difference between revisions

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-[[Image:1pty.jpg|left|200px]]<br /><applet load="1pty" size="350" 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/>
-PTY 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 <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=PTR:'>PTR</scene> 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://oca.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: 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://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:32:29 2008''