View source for 3zv2


==Human protein-tyrosine phosphatase 1b C215A, S216A mutant==
<StructureSection load='3zv2' size='340' side='right'caption='[[3zv2]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zv2]] 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=3ZV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZV2 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]] 2.8&#8491;</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=3zv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zv2 OCA], [https://pdbe.org/3zv2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zv2 RCSB], [https://www.ebi.ac.uk/pdbsum/3zv2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zv2 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein tyrosine phosphatase 1B (PTP1B) plays important roles in downregulation of insulin and leptin signaling and is an established therapeutic target for diabetes and obesity. PTP1B is regulated by reactive oxygen species (ROS) produced in response to various stimuli, including insulin. The reversibly oxidized form of the enzyme (PTP1B-OX) is inactive and undergoes profound conformational changes at the active site. We generated conformation-sensor antibodies, in the form of single-chain variable fragments (scFvs), that stabilize PTP1B-OX and thereby inhibit its phosphatase function. Expression of conformation-sensor scFvs as intracellular antibodies (intrabodies) enhanced insulin-induced tyrosyl phosphorylation of the beta subunit of the insulin receptor and its substrate IRS-1 and increased insulin-induced phosphorylation of PKB/AKT. Our data suggest that stabilization of the oxidized, inactive form of PTP1B with appropriate therapeutic molecules may offer a paradigm for phosphatase drug development.

Conformation-Sensing Antibodies Stabilize the Oxidized Form of PTP1B and Inhibit Its Phosphatase Activity.,Haque A, Andersen JN, Salmeen A, Barford D, Tonks NK Cell. 2011 Sep 30;147(1):185-98. PMID:21962515<ref>PMID:21962515</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3zv2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Barford D]]
[[Category: Salmeen A]]
[[Category: Tonks NK]]