This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1nwe

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /> <applet load="1nwe" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nwe, resolution 3.10&Aring;" /> '''Ptp1B R47C Modified...)
Current revision (06:09, 3 April 2024) (edit) (undo)
 
(17 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1nwe.gif|left|200px]]<br />
 
-
<applet load="1nwe" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1nwe, resolution 3.10&Aring;" />
 
-
'''Ptp1B R47C Modified at C47 with N-[4-(2-{2-[3-(2-Bromo-acetylamino)-propionylamino]-3-hydroxy-propionylamino}-ethyl)-phenyl]-oxalamic acid'''<br />
 
-
==Overview==
+
==Ptp1B R47C Modified at C47 with N-[4-(2-{2-[3-(2-Bromo-acetylamino)-propionylamino]-3-hydroxy-propionylamino}-ethyl)-phenyl]-oxalamic acid==
-
Protein tyrosine phosphatases play important roles in many signaling cascades involved in human disease. The identification of druglike inhibitors for these targets is a major challenge, and the discovery of suitable phosphotyrosine (pY) mimetics remains one of the key difficulties. Here we describe an extension of tethering technology, "breakaway tethering", which is ideally suited for discovering such new chemical entities. The approach involves first irreversibly modifying a protein with an extender that contains both a masked thiol and a known pY mimetic. The extender is then cleaved to release the pY mimetic, unmasking the thiol. The resulting protein is screened against a library of disulfide-containing small molecule fragments; any molecules with inherent affinity for the pY binding site will preferentially form disulfides with the extender, allowing for their identification by mass spectrometry. The ability to start from a known substrate mimimizes perturbation of protein structure and increases the opportunity to probe the active site using tethering. We applied this approach to the anti-diabetic protein PTP1B to discover a pY mimetic which belongs to a new molecular class and which binds in a novel fashion.
+
<StructureSection load='1nwe' size='340' side='right'caption='[[1nwe]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1nwe]] 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=1NWE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NWE 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]] 3.1&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FG1:N-[4-(2-{2-[3-(2-BROMO-ACETYLAMINO)-PROPIONYLAMINO]-3-HYDROXY-PROPIONYLAMINO}-ETHYL)-PHENYL]-OXALAMIC+ACID'>FG1</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=1nwe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nwe OCA], [https://pdbe.org/1nwe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nwe RCSB], [https://www.ebi.ac.uk/pdbsum/1nwe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nwe 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/nw/1nwe_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=1nwe 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/>
-
1NWE 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 FG1 as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1NWE OCA].
+
__TOC__
-
 
+
</StructureSection>
-
==Reference==
+
-
Discovery of a new phosphotyrosine mimetic for PTP1B using breakaway tethering., Erlanson DA, McDowell RS, He MM, Randal M, Simmons RL, Kung J, Waight A, Hansen SK, J Am Chem Soc. 2003 May 14;125(19):5602-3. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12733877 12733877]
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Protein-tyrosine-phosphatase]]
+
[[Category: Large Structures]]
-
[[Category: Single protein]]
+
[[Category: Erlanson DA]]
-
[[Category: Erlanson, D.A.]]
+
[[Category: Hansen SK]]
-
[[Category: Hansen, S.K.]]
+
[[Category: He MM]]
-
[[Category: He, M.M.]]
+
[[Category: Kung J]]
-
[[Category: Kung, J.]]
+
[[Category: McDowell RS]]
-
[[Category: McDowell, R.S.]]
+
[[Category: Randal M]]
-
[[Category: Randal, M.]]
+
[[Category: Simmons RL]]
-
[[Category: Simmons, R.L.]]
+
[[Category: Waight A]]
-
[[Category: Waight, A.]]
+
-
[[Category: FG1]]
+
-
[[Category: acetylation]]
+
-
[[Category: hydrolase]]
+
-
[[Category: phospatase]]
+
-
[[Category: phosphorylation]]
+
-
[[Category: phosphotyrosine mimetic]]
+
-
 
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:26:36 2007''
+

Current revision

Ptp1B R47C Modified at C47 with N-[4-(2-{2-[3-(2-Bromo-acetylamino)-propionylamino]-3-hydroxy-propionylamino}-ethyl)-phenyl]-oxalamic acid

PDB ID 1nwe

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1nwe"
Personal tools