View source for 3o4t


==Crystal Structure of HePTP with an Open WPD Loop and Partially Depleted Active Site==
<StructureSection load='3o4t' size='340' side='right'caption='[[3o4t]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3o4t]] 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=3O4T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O4T 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</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=3o4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o4t OCA], [https://pdbe.org/3o4t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o4t RCSB], [https://www.ebi.ac.uk/pdbsum/3o4t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o4t ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PTN7_HUMAN PTN7_HUMAN] Protein phosphatase that acts preferentially on tyrosine-phosphorylated MAPK1. Plays a role in the regulation of T and B-lymphocyte development and signal transduction.<ref>PMID:1510684</ref> <ref>PMID:1530918</ref> <ref>PMID:9624114</ref> <ref>PMID:10206983</ref> <ref>PMID:10559944</ref> <ref>PMID:10702794</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Phosphotyrosine hydrolysis by protein tyrosine phosphatases (PTPs) involves substrate binding by the PTP loop and closure over the active site by the WPD loop. The E loop, located immediately adjacent to the PTP and WPD loops, is conserved among human PTPs in both sequence and structure, yet the role of this loop in substrate binding and catalysis is comparatively unexplored. Hematopoietic PTP (HePTP) is a member of the kinase interaction motif (KIM) PTP family. Compared to other PTPs, KIM-PTPs have E loops that are unique in both sequence and structure. In order to understand the role of the E loop in the transition between the closed state and the open state of HePTP, we identified a novel crystal form of HePTP that allowed the closed-state-to-open-state transition to be observed within a single crystal form. These structures, which include the first structure of the HePTP open state, show that the WPD loop adopts an 'atypically open' conformation and, importantly, that ligands can be exchanged at the active site, which is critical for HePTP inhibitor development. These structures also show that tetrahedral oxyanions bind at a novel secondary site and function to coordinate the PTP, WPD, and E loops. Finally, using both structural and kinetic data, we reveal a novel role for E-loop residue Lys182 in enhancing HePTP catalytic activity through its interaction with Asp236 of the WPD loop, providing the first evidence for the coordinated dynamics of the WPD and E loops in the catalytic cycle, which, as we show, is relevant to multiple PTP families.

Visualizing Active-Site Dynamics in Single Crystals of HePTP: Opening of the WPD Loop Involves Coordinated Movement of the E Loop.,Critton DA, Tautz L, Page R J Mol Biol. 2010 Nov 19. PMID:21094165<ref>PMID:21094165</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3o4t" 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: Critton DA]]
[[Category: Page R]]