7kh8
From Proteopedia
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==Human LMPTP in complex with inhibitor== | ==Human LMPTP in complex with inhibitor== | ||
| - | <StructureSection load='7kh8' size='340' side='right'caption='[[7kh8]]' scene=''> | + | <StructureSection load='7kh8' size='340' side='right'caption='[[7kh8]], [[Resolution|resolution]] 1.30Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KH8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KH8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7kh8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KH8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KH8 FirstGlance]. <br> |
| - | </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=7kh8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kh8 OCA], [https://pdbe.org/7kh8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kh8 RCSB], [https://www.ebi.ac.uk/pdbsum/7kh8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kh8 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=WE7:3-[(2,6-dichlorophenyl)methyl]-8-(2-methylphenyl)-3H-purin-6-amine'>WE7</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACP1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=7kh8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kh8 OCA], [https://pdbe.org/7kh8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kh8 RCSB], [https://www.ebi.ac.uk/pdbsum/7kh8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kh8 ProSAT]</span></td></tr> | ||
</table> | </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 == | ||
| + | Obesity-associated insulin resistance plays a central role in the pathogenesis of type 2 diabetes. A promising approach to decrease insulin resistance in obesity is to inhibit the protein tyrosine phosphatases that negatively regulate insulin receptor signaling. The low-molecular-weight protein tyrosine phosphatase (LMPTP) acts as a critical promoter of insulin resistance in obesity by inhibiting phosphorylation of the liver insulin receptor activation motif. Here, we report development of a novel purine-based chemical series of LMPTP inhibitors. These compounds inhibit LMPTP with an uncompetitive mechanism and are highly selective for LMPTP over other protein tyrosine phosphatases. We also report the generation of a highly orally bioavailable purine-based analogue that reverses obesity-induced diabetes in mice. | ||
| + | |||
| + | Discovery of Orally Bioavailable Purine-Based Inhibitors of the Low-Molecular-Weight Protein Tyrosine Phosphatase.,Stanford SM, Diaz MA, Ardecky RJ, Zou J, Roosild T, Holmes ZJ, Nguyen TP, Hedrick MP, Rodiles S, Guan A, Grotegut S, Santelli E, Chung TDY, Jackson MR, Bottini N, Pinkerton AB J Med Chem. 2021 May 13;64(9):5645-5653. doi: 10.1021/acs.jmedchem.0c02126. Epub , 2021 Apr 29. PMID:33914534<ref>PMID:33914534</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7kh8" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Ardecky | + | [[Category: Ardecky, R J]] |
| - | [[Category: Bottini N]] | + | [[Category: Bottini, N]] |
| - | [[Category: Chung | + | [[Category: Chung, T D.Y]] |
| - | [[Category: Diaz | + | [[Category: Diaz, M A]] |
| - | [[Category: Hedrick | + | [[Category: Hedrick, M P]] |
| - | [[Category: Holmes | + | [[Category: Holmes, Z J]] |
| - | [[Category: Jackson | + | [[Category: Jackson, M R]] |
| - | [[Category: Pinkerton | + | [[Category: Pinkerton, A B]] |
| - | [[Category: Rodiles S]] | + | [[Category: Rodiles, S]] |
| - | [[Category: Roosild T]] | + | [[Category: Roosild, T]] |
| - | [[Category: Santelli E]] | + | [[Category: Santelli, E]] |
| - | [[Category: Stanford | + | [[Category: Stanford, S M]] |
| - | [[Category: Zou J]] | + | [[Category: Zou, J]] |
| + | [[Category: Complex]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Lmwptp]] | ||
| + | [[Category: Protein tyrosine phosphatase]] | ||
Revision as of 09:28, 26 May 2021
Human LMPTP in complex with inhibitor
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Categories: Human | Large Structures | Ardecky, R J | Bottini, N | Chung, T D.Y | Diaz, M A | Hedrick, M P | Holmes, Z J | Jackson, M R | Pinkerton, A B | Rodiles, S | Roosild, T | Santelli, E | Stanford, S M | Zou, J | Complex | Hydrolase | Hydrolase-hydrolase inhibitor complex | Inhibitor | Lmwptp | Protein tyrosine phosphatase
