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.


1q1m

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:54, 16 August 2023) (edit) (undo)
 
(13 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1q1m.jpg|left|200px]]
 
-
{{Structure
+
==A Highly Efficient Approach to a Selective and Cell Active PTP1B inhibitors==
-
|PDB= 1q1m |SIZE=350|CAPTION= <scene name='initialview01'>1q1m</scene>, resolution 2.60&Aring;
+
<StructureSection load='1q1m' size='340' side='right'caption='[[1q1m]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
-
|SITE=
+
== Structural highlights ==
-
|LIGAND= <scene name='pdbligand=234:5-{2-FLUORO-5-[3-(3-HYDROXY-2-METHOXYCARBONYL-PHENOXY)-PROPENYL]-PHENYL}-ISOXAZOLE-3-CARBOXYLIC ACID'>234</scene>
+
<table><tr><td colspan='2'>[[1q1m]] 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=1Q1M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q1M FirstGlance]. <br>
-
|ACTIVITY= [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]
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
-
|GENE= PTPN1 OR PTP1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=234:5-{2-FLUORO-5-[3-(3-HYDROXY-2-METHOXYCARBONYL-PHENOXY)-PROPENYL]-PHENYL}-ISOXAZOLE-3-CARBOXYLIC+ACID'>234</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=1q1m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q1m OCA], [https://pdbe.org/1q1m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q1m RCSB], [https://www.ebi.ac.uk/pdbsum/1q1m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q1m ProSAT]</span></td></tr>
-
 
+
</table>
-
'''A Highly Efficient Approach to a Selective and Cell Active PTP1B inhibitors'''
+
== 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 ==
-
==Overview==
+
[[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/q1/1q1m_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=1q1m ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
Using an NMR-based fragment screening and X-ray crystal structure-based assembly, starting with millimolar ligands for both the catalytic site and the second phosphotyrosine binding site, we have identified a small-molecule inhibitor of protein tyrosine phosphatase 1B with low micromolar inhibition constant, high selectivity (30-fold) over the highly homologous T-cell protein tyrosine phosphatase, and good cellular activity in COS-7 cells.
Using an NMR-based fragment screening and X-ray crystal structure-based assembly, starting with millimolar ligands for both the catalytic site and the second phosphotyrosine binding site, we have identified a small-molecule inhibitor of protein tyrosine phosphatase 1B with low micromolar inhibition constant, high selectivity (30-fold) over the highly homologous T-cell protein tyrosine phosphatase, and good cellular activity in COS-7 cells.
-
==Disease==
+
Fragment screening and assembly: a highly efficient approach to a selective and cell active protein tyrosine phosphatase 1B inhibitor.,Liu G, Xin Z, Pei Z, Hajduk PJ, Abad-Zapatero C, Hutchins CW, Zhao H, Lubben TH, Ballaron SJ, Haasch DL, Kaszubska W, Rondinone CM, Trevillyan JM, Jirousek MR J Med Chem. 2003 Sep 25;46(20):4232-5. PMID:13678400<ref>PMID:13678400</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>
-
1Q1M is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q1M OCA].
+
</div>
 +
<div class="pdbe-citations 1q1m" style="background-color:#fffaf0;"></div>
-
==Reference==
+
==See Also==
-
Fragment screening and assembly: a highly efficient approach to a selective and cell active protein tyrosine phosphatase 1B inhibitor., Liu G, Xin Z, Pei Z, Hajduk PJ, Abad-Zapatero C, Hutchins CW, Zhao H, Lubben TH, Ballaron SJ, Haasch DL, Kaszubska W, Rondinone CM, Trevillyan JM, Jirousek MR, J Med Chem. 2003 Sep 25;46(20):4232-5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/13678400 13678400]
+
*[[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: Haasch DL]]
-
[[Category: Haasch, D L.]]
+
[[Category: Hajduk PJ]]
-
[[Category: Hajduk, P J.]]
+
[[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: Trevillyan JM]]
-
[[Category: Trevillyan, J M.]]
+
[[Category: Xin Z]]
-
[[Category: Xin, Z.]]
+
[[Category: Zhao H]]
-
[[Category: Zhao, H.]]
+
-
[[Category: 234]]
+
-
[[Category: inhibitors with isoxazole-salicylate pharmacophore]]
+
-
[[Category: protein tyrosine phosphatase 1b]]
+
-
[[Category: ptp1b]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:31:49 2008''
+

Current revision

A Highly Efficient Approach to a Selective and Cell Active PTP1B inhibitors

PDB ID 1q1m

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/1q1m"
Personal tools