5ow1: Difference between revisions
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==X-Ray Characterization of Striatal-Enriched Protein Tyrosine Phosphatase Inhibitors== | ==X-Ray Characterization of Striatal-Enriched Protein Tyrosine Phosphatase Inhibitors== | ||
<StructureSection load='5ow1' size='340' side='right' caption='[[5ow1]], [[Resolution|resolution]] 2.05Å' scene=''> | <StructureSection load='5ow1' size='340' side='right'caption='[[5ow1]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ow1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OW1 OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5ow1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OW1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5OW1 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AY8:[[3-(3-cyclohexyl-2-oxidanyl-phenyl)phenyl]-bis(fluoranyl)methyl]phosphonic+acid'>AY8</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AY8:[[3-(3-cyclohexyl-2-oxidanyl-phenyl)phenyl]-bis(fluoranyl)methyl]phosphonic+acid'>AY8</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSS:S-MERCAPTOCYSTEINE'>CSS</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSS:S-MERCAPTOCYSTEINE'>CSS</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ovr|5ovr]], [[5ovx|5ovx]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ovr|5ovr]], [[5ovx|5ovx]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPN5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ow1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ow1 OCA], [http://pdbe.org/5ow1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ow1 RCSB], [http://www.ebi.ac.uk/pdbsum/5ow1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ow1 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5ow1" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5ow1" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Protein-tyrosine-phosphatase]] | [[Category: Protein-tyrosine-phosphatase]] | ||
[[Category: Kack, H]] | [[Category: Kack, H]] | ||
Revision as of 10:32, 2 September 2020
X-Ray Characterization of Striatal-Enriched Protein Tyrosine Phosphatase InhibitorsX-Ray Characterization of Striatal-Enriched Protein Tyrosine Phosphatase Inhibitors
Structural highlights
Function[PTN5_HUMAN] May regulate the activity of several effector molecules involved in synaptic plasticity and neuronal cell survival, including MAPKs, Src family kinases and NMDA receptors.[1] Publication Abstract from PubMedExcessive activity of striatal-enriched protein tyrosine phosphatase (STEP) in the brain has been detected in numerous neuropsychiatric disorders including Alzheimer's disease. Notably, knockdown of STEP in an Alzheimer mouse model effected an increase in the phosphorylation levels of downstream STEP substrates and a significant reversal in the observed cognitive and memory deficits. These data point to the promising potential of STEP as a target for drug discovery in Alzheimer's treatment. We previously reported a substrate-based approach to the development of low molecular weight STEP inhibitors with Ki values as low as 7.8 muM. Herein, we disclose the first X-ray crystal structures of inhibitors bound to STEP and the surprising finding that they occupy noncoincident binding sites. Moreover, we utilize this structural information to optimize the inhibitor structure to achieve a Ki of 110 nM, with 15-60-fold selectivity across a series of phosphatases. X-ray Characterization and Structure-Based Optimization of Striatal-Enriched Protein Tyrosine Phosphatase Inhibitors.,Witten MR, Wissler L, Snow M, Geschwindner S, Read JA, Brandon NJ, Nairn AC, Lombroso PJ, Kack H, Ellman JA J Med Chem. 2017 Nov 8. doi: 10.1021/acs.jmedchem.7b01292. PMID:29116812[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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