5kql: Difference between revisions
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==Co-crystal structure of LMW-PTP in complex with 2-oxo-1-phenyl-2-(phenylamino)ethanesulfonic acid== | |||
<StructureSection load='5kql' size='340' side='right'caption='[[5kql]], [[Resolution|resolution]] 1.45Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5kql]] 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=5KQL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KQL 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]] 1.45Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6VY:(1~{S})-2-OXIDANYLIDENE-1-PHENYL-2-PHENYLAZANYL-ETHANESULFONIC+ACID'>6VY</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=5kql FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kql OCA], [https://pdbe.org/5kql PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kql RCSB], [https://www.ebi.ac.uk/pdbsum/5kql PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kql ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PPAC_HUMAN PPAC_HUMAN] Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates. Isoform 3 does not possess phosphatase activity. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The low molecular weight protein tyrosine phosphatase (LMW-PTP) is a regulator of a number of signaling pathways and has been implicated as a potential target for oncology and diabetes/obesity. There is significant therapeutic interest in developing potent and selective inhibitors to control LMW-PTP activity. We report the discovery of a novel class of LMW-PTP inhibitors derived from sulfophenyl acetic amide (SPAA), some of which exhibit greater than 50-fold preference for LMW-PTP over a large panel of PTPs. X-ray crystallography reveals that binding of SPAA-based inhibitors induces a striking conformational change in the LMW-PTP active site, leading to the formation of a previously undisclosed hydrophobic pocket to accommodate the alpha-phenyl ring in the ligand. This induced-fit mechanism is likely a major contributor responsible for the exquisite inhibitor selectivity. | |||
Inhibition of Low Molecular Weight Protein Tyrosine Phosphatase by an Induced-Fit Mechanism.,He R, Wang J, Yu ZH, Zhang RY, Liu S, Wu L, Zhang ZY J Med Chem. 2016 Oct 3. PMID:27676368<ref>PMID:27676368</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5kql" style="background-color:#fffaf0;"></div> | ||
[[Category: Wang | |||
[[Category: Zhang | ==See Also== | ||
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Wang J]] | |||
[[Category: Yu Z-H]] | |||
[[Category: Zhang Z-Y]] | |||
Latest revision as of 13:51, 27 September 2023
Co-crystal structure of LMW-PTP in complex with 2-oxo-1-phenyl-2-(phenylamino)ethanesulfonic acidCo-crystal structure of LMW-PTP in complex with 2-oxo-1-phenyl-2-(phenylamino)ethanesulfonic acid
Structural highlights
FunctionPPAC_HUMAN Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates. Isoform 3 does not possess phosphatase activity. Publication Abstract from PubMedThe low molecular weight protein tyrosine phosphatase (LMW-PTP) is a regulator of a number of signaling pathways and has been implicated as a potential target for oncology and diabetes/obesity. There is significant therapeutic interest in developing potent and selective inhibitors to control LMW-PTP activity. We report the discovery of a novel class of LMW-PTP inhibitors derived from sulfophenyl acetic amide (SPAA), some of which exhibit greater than 50-fold preference for LMW-PTP over a large panel of PTPs. X-ray crystallography reveals that binding of SPAA-based inhibitors induces a striking conformational change in the LMW-PTP active site, leading to the formation of a previously undisclosed hydrophobic pocket to accommodate the alpha-phenyl ring in the ligand. This induced-fit mechanism is likely a major contributor responsible for the exquisite inhibitor selectivity. Inhibition of Low Molecular Weight Protein Tyrosine Phosphatase by an Induced-Fit Mechanism.,He R, Wang J, Yu ZH, Zhang RY, Liu S, Wu L, Zhang ZY J Med Chem. 2016 Oct 3. PMID:27676368[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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