View source for 6h8s


==CRYSTAL STRUCTURE OF THE MOUSE PROTEIN TYROSINE PHOSPHATASE PTPN5 (STEP) IN COMPLEX WITH COMPOUND BI-0314==
<StructureSection load='6h8s' size='340' side='right' caption='[[6h8s]], [[Resolution|resolution]] 1.77&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6h8s]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H8S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H8S FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FSZ:1-[3-piperidin-4-yl-5-(trifluoromethyl)phenyl]guanidine'>FSZ</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6h8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h8s OCA], [http://pdbe.org/6h8s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h8s RCSB], [http://www.ebi.ac.uk/pdbsum/6h8s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h8s ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/PTN5_MOUSE PTN5_MOUSE]] May regulate the activity of several effector molecules involved in synaptic plasticity and neuronal cell survival, including MAPKs, Src family kinases and NMDA receptors. 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein tyrosine phosphatase non-receptor type 5 (PTPN5, STEP) is a brain specific phosphatase that regulates synaptic function and plasticity by modulation of N-methyl-d-aspartate receptor (NMDAR) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking. Dysregulation of STEP has been linked to neurodegenerative and neuropsychiatric diseases, highlighting this enzyme as an attractive therapeutic target for drug discovery. Selective targeting of STEP with small molecules has been hampered by high conservation of the active site among protein tyrosine phosphatases. We report the discovery of the first small molecule allosteric activator for STEP that binds to the phosphatase domain. Allosteric binding is confirmed by both X-ray and (15)N NMR experiments, and specificity has been demonstrated by an enzymatic test cascade. Molecular dynamics simulations indicate stimulation of enzymatic activity by a long-range allosteric mechanism. To allow the scientific community to make use of this tool, we offer to provide the compound in the course of an open innovation initiative.

Allosteric Activation of Striatal-Enriched Protein Tyrosine Phosphatase (STEP, PTPN5) by a Fragment-like Molecule.,Tautermann CS, Binder F, Buttner FH, Eickmeier C, Fiegen D, Gross U, Grundl MA, Heilker R, Hobson S, Hoerer S, Luippold A, Mack V, Montel F, Peters S, Bhattacharya S, Vaidehi N, Schnapp G, Thamm S, Zeeb M J Med Chem. 2018 Sep 12. doi: 10.1021/acs.jmedchem.8b00857. PMID:30207464<ref>PMID:30207464</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6h8s" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Protein-tyrosine-phosphatase]]
[[Category: Fiegen, D]]
[[Category: Schnapp, G]]
[[Category: Allosteric modulator]]
[[Category: Hydrolase]]
[[Category: Protein phosphatase]]
[[Category: Ptn5]]
[[Category: Step]]