1nz7: Difference between revisions

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{{Seed}}
[[Image:1nz7.png|left|200px]]


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==POTENT, SELECTIVE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B USING A SECOND PHOSPHOTYROSINE BINDING SITE, complexed with compound 19.==
The line below this paragraph, containing "STRUCTURE_1nz7", creates the "Structure Box" on the page.
<StructureSection load='1nz7' size='340' side='right'caption='[[1nz7]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1nz7]] 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=1NZ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NZ7 FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
-->
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=901:2-[(4-{2-ACETYLAMINO-2-[4-(1-CARBOXY-3-METHYLSULFANYL-PROPYLCARBAMOYL)-BUTYLCARBAMOYL]-ETHYL}-2-ETHYL-PHENYL)-OXALYL-AMINO]-BENZOIC+ACID'>901</scene></td></tr>
{{STRUCTURE_1nz7|  PDB=1nz7  |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1nz7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nz7 OCA], [https://pdbe.org/1nz7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nz7 RCSB], [https://www.ebi.ac.uk/pdbsum/1nz7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nz7 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/nz/1nz7_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=1nz7 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We have previously reported a novel series of oxalyl-aryl-amino benzoic acid-based, catalytic site-directed, competitive, reversible protein tyrosine phosphatase 1B (PTP1B) inhibitors. With readily access to key intermediates, we utilized a solution phase parallel synthesis approach and rapidly identified a highly potent PTP1B inhibitor (19, K(i)=76 nM) with moderate selectivity (5-fold) over T-cell PTPase (TCPTP) through interacting with a second phosphotyrosine binding site (site 2) in the close proximity to the catalytic site.


===POTENT, SELECTIVE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B USING A SECOND PHOSPHOTYROSINE BINDING SITE, complexed with compound 19.===
Potent, selective inhibitors of protein tyrosine phosphatase 1B.,Xin Z, Oost TK, Abad-Zapatero C, Hajduk PJ, Pei Z, Szczepankiewicz BG, Hutchins CW, Ballaron SJ, Stashko MA, Lubben T, Trevillyan JM, Jirousek MR, Liu G Bioorg Med Chem Lett. 2003 Jun 2;13(11):1887-90. PMID:12749891<ref>PMID:12749891</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1nz7" style="background-color:#fffaf0;"></div>


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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_12749891}}, adds the Publication Abstract to the page
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 12749891 is the PubMed ID number.
== References ==
-->
<references/>
{{ABSTRACT_PUBMED_12749891}}
__TOC__
 
</StructureSection>
==About this Structure==
1NZ7 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=1NZ7 OCA].
 
==Reference==
Potent, selective inhibitors of protein tyrosine phosphatase 1B., Xin Z, Oost TK, Abad-Zapatero C, Hajduk PJ, Pei Z, Szczepankiewicz BG, Hutchins CW, Ballaron SJ, Stashko MA, Lubben T, Trevillyan JM, Jirousek MR, Liu G, Bioorg Med Chem Lett. 2003 Jun 2;13(11):1887-90. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12749891 12749891]
[[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: Hutchins CW]]
[[Category: Hutchins, C W.]]
[[Category: Jirousek MR]]
[[Category: Jirousek, M R.]]
[[Category: Liu G]]
[[Category: Liu, G.]]
[[Category: Lubben T]]
[[Category: Lubben, T.]]
[[Category: Oost TK]]
[[Category: Oost, T K.]]
[[Category: Pei Z]]
[[Category: Pei, Z.]]
[[Category: Stashko MA]]
[[Category: Stashko, M A.]]
[[Category: Szczepankiewicz BG]]
[[Category: Szczepankiewicz, B G.]]
[[Category: Trevillyan JM]]
[[Category: Trevillyan, J M.]]
[[Category: Xin Z]]
[[Category: Xin, Z.]]
[[Category: Oxamic acid inhibitor bound to p-loop]]
[[Category: Protein tyrosine phosphatase fold]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 09:51:19 2008''

Latest revision as of 12:27, 16 August 2023

POTENT, SELECTIVE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B USING A SECOND PHOSPHOTYROSINE BINDING SITE, complexed with compound 19.POTENT, SELECTIVE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B USING A SECOND PHOSPHOTYROSINE BINDING SITE, complexed with compound 19.

Structural highlights

1nz7 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 2.4Å
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.

Publication Abstract from PubMed

We have previously reported a novel series of oxalyl-aryl-amino benzoic acid-based, catalytic site-directed, competitive, reversible protein tyrosine phosphatase 1B (PTP1B) inhibitors. With readily access to key intermediates, we utilized a solution phase parallel synthesis approach and rapidly identified a highly potent PTP1B inhibitor (19, K(i)=76 nM) with moderate selectivity (5-fold) over T-cell PTPase (TCPTP) through interacting with a second phosphotyrosine binding site (site 2) in the close proximity to the catalytic site.

Potent, selective inhibitors of protein tyrosine phosphatase 1B.,Xin Z, Oost TK, Abad-Zapatero C, Hajduk PJ, Pei Z, Szczepankiewicz BG, Hutchins CW, Ballaron SJ, Stashko MA, Lubben T, Trevillyan JM, Jirousek MR, Liu G Bioorg Med Chem Lett. 2003 Jun 2;13(11):1887-90. PMID:12749891[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
  3. ↑ Xin Z, Oost TK, Abad-Zapatero C, Hajduk PJ, Pei Z, Szczepankiewicz BG, Hutchins CW, Ballaron SJ, Stashko MA, Lubben T, Trevillyan JM, Jirousek MR, Liu G. Potent, selective inhibitors of protein tyrosine phosphatase 1B. Bioorg Med Chem Lett. 2003 Jun 2;13(11):1887-90. PMID:12749891

1nz7, resolution 2.40Å

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