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.


1xbo

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (06:43, 23 August 2023) (edit) (undo)
 
(16 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1xbo.jpg|left|200px]]<br /><applet load="1xbo" size="350" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1xbo, resolution 2.50&Aring;" />
 
-
'''PTP1B complexed with Isoxazole Carboxylic Acid'''<br />
 
-
==Overview==
+
==PTP1B complexed with Isoxazole Carboxylic Acid==
-
Guided by X-ray crystallography, we have extended the structure-activity, relationship (SAR) study on an isoxazole carboxylic acid-based PTP1B, inhibitor (1) and more potent and equally selective (&gt;20-fold selectivity, over the highly homologous T-cell PTPase, TCPTP) PTP1B inhibitors were, identified. Inhibitor 7 demonstrated good cellular activity against PTP1B, in COS 7 cells.
+
<StructureSection load='1xbo' size='340' side='right'caption='[[1xbo]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1xbo]] 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=1XBO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XBO 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]] 2.5&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IX1:5-(3-{3-[3-HYDROXY-2-(METHOXYCARBONYL)PHENOXY]PROPENYL}PHENYL)-4-(HYDROXYMETHYL)ISOXAZOLE-3-CARBOXYLIC+ACID'>IX1</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=1xbo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xbo OCA], [https://pdbe.org/1xbo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xbo RCSB], [https://www.ebi.ac.uk/pdbsum/1xbo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xbo 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/xb/1xbo_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=1xbo ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Guided by X-ray crystallography, we have extended the structure-activity relationship (SAR) study on an isoxazole carboxylic acid-based PTP1B inhibitor (1) and more potent and equally selective (&gt;20-fold selectivity over the highly homologous T-cell PTPase, TCPTP) PTP1B inhibitors were identified. Inhibitor 7 demonstrated good cellular activity against PTP1B in COS 7 cells.
-
==Disease==
+
Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors.,Zhao H, Liu G, Xin Z, Serby MD, Pei Z, Szczepankiewicz BG, Hajduk PJ, Abad-Zapatero C, Hutchins CW, Lubben TH, Ballaron SJ, Haasch DL, Kaszubska W, Rondinone CM, Trevillyan JM, Jirousek MR Bioorg Med Chem Lett. 2004 Nov 15;14(22):5543-6. PMID:15482920<ref>PMID:15482920</ref>
-
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]]
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
1XBO 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=IX1:'>IX1</scene> 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://oca.weizmann.ac.il/oca-bin/ocashort?id=1XBO OCA].
+
</div>
 +
<div class="pdbe-citations 1xbo" style="background-color:#fffaf0;"></div>
-
==Reference==
+
==See Also==
-
Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors., Zhao H, Liu G, Xin Z, Serby MD, Pei Z, Szczepankiewicz BG, Hajduk PJ, Abad-Zapatero C, Hutchins CW, Lubben TH, Ballaron SJ, Haasch DL, Kaszubska W, Rondinone CM, Trevillyan JM, Jirousek MR, Bioorg Med Chem Lett. 2004 Nov 15;14(22):5543-6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15482920 15482920]
+
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Protein-tyrosine-phosphatase]]
+
[[Category: Large Structures]]
-
[[Category: Single protein]]
+
[[Category: Abad-Zapatero C]]
-
[[Category: Abad-Zapatero, C.]]
+
[[Category: Ballaron SJ]]
-
[[Category: Ballaron, S.J.]]
+
[[Category: Hajduk PJ]]
-
[[Category: Hajduk, P.J.]]
+
[[Category: Hassach DL]]
-
[[Category: Hassach, D.L.]]
+
[[Category: Hutchins CW]]
-
[[Category: Hutchins, C.W.]]
+
[[Category: Jirousek MR]]
-
[[Category: Jirousek, M.R.]]
+
[[Category: Kaszubska W]]
-
[[Category: Kaszubska, W.]]
+
[[Category: Liu G]]
-
[[Category: Liu, G.]]
+
[[Category: Lubben TH]]
-
[[Category: Lubben, T.H.]]
+
[[Category: Pei Z]]
-
[[Category: Pei, Z.]]
+
[[Category: Rondinone CM]]
-
[[Category: Rondinone, C.M.]]
+
[[Category: Serby M]]
-
[[Category: Serby, M.]]
+
[[Category: Szczepankiewicz BG]]
-
[[Category: Szczepankiewicz, B.G.]]
+
[[Category: Trevillyan JM]]
-
[[Category: Trevillyan, J.M.]]
+
[[Category: Xin Z]]
-
[[Category: Xin, Z.]]
+
[[Category: Zhao H]]
-
[[Category: Zhao, H.]]
+
-
[[Category: IX1]]
+
-
[[Category: isoxazole carboxylic acid]]
+
-
[[Category: protein tyrosine phosphatase 1b]]
+
-
[[Category: ptp1b]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:08:53 2008''
+

Current revision

PTP1B complexed with Isoxazole Carboxylic Acid

PDB ID 1xbo

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/1xbo"
Personal tools