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| | <StructureSection load='5jnt' size='340' side='right'caption='[[5jnt]], [[Resolution|resolution]] 1.45Å' scene=''> | | <StructureSection load='5jnt' size='340' side='right'caption='[[5jnt]], [[Resolution|resolution]] 1.45Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jnt]] 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=5JNT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JNT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jnt]] 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=5JNT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JNT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr> | + | </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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jnr|5jnr]], [[5jns|5jns]], [[5jnu|5jnu]], [[5jnv|5jnv]], [[5jnw|5jnw]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACP1 ([http://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=5jnt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jnt OCA], [https://pdbe.org/5jnt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jnt RCSB], [https://www.ebi.ac.uk/pdbsum/5jnt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jnt ProSAT]</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5jnt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jnt OCA], [http://pdbe.org/5jnt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jnt RCSB], [http://www.ebi.ac.uk/pdbsum/5jnt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jnt ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Protein-tyrosine-phosphatase]]
| + | [[Category: Aleshin AE]] |
| - | [[Category: Aleshin, A E]] | + | [[Category: Bankston L]] |
| - | [[Category: Bankston, L]] | + | [[Category: Bottini N]] |
| - | [[Category: Bottini, N]] | + | [[Category: Cadwell G]] |
| - | [[Category: Cadwell, G]] | + | [[Category: Liddington RC]] |
| - | [[Category: Liddington, R C]] | + | [[Category: Stanford SM]] |
| - | [[Category: Stanford, S M]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lmptp]]
| + | |
| - | [[Category: Lmw-ptp]]
| + | |
| - | [[Category: Protein tyrosine phosphatase]]
| + | |
| Structural highlights
Function
PPAC_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 PubMed
Obesity-associated insulin resistance plays a central role in type 2 diabetes. As such, tyrosine phosphatases that dephosphorylate the insulin receptor (IR) are potential therapeutic targets. The low-molecular-weight protein tyrosine phosphatase (LMPTP) is a proposed IR phosphatase, yet its role in insulin signaling in vivo has not been defined. Here we show that global and liver-specific LMPTP deletion protects mice from high-fat diet-induced diabetes without affecting body weight. To examine the role of the catalytic activity of LMPTP, we developed a small-molecule inhibitor with a novel uncompetitive mechanism, a unique binding site at the opening of the catalytic pocket, and an exquisite selectivity over other phosphatases. This inhibitor is orally bioavailable, and it increases liver IR phosphorylation in vivo and reverses high-fat diet-induced diabetes. Our findings suggest that LMPTP is a key promoter of insulin resistance and that LMPTP inhibitors would be beneficial for treating type 2 diabetes.
Diabetes reversal by inhibition of the low-molecular-weight tyrosine phosphatase.,Stanford SM, Aleshin AE, Zhang V, Ardecky RJ, Hedrick MP, Zou J, Ganji SR, Bliss MR, Yamamoto F, Bobkov AA, Kiselar J, Liu Y, Cadwell GW, Khare S, Yu J, Barquilla A, Chung TD, Mustelin T, Schenk S, Bankston LA, Liddington RC, Pinkerton AB, Bottini N Nat Chem Biol. 2017 Mar 27. doi: 10.1038/nchembio.2344. PMID:28346406[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Stanford SM, Aleshin AE, Zhang V, Ardecky RJ, Hedrick MP, Zou J, Ganji SR, Bliss MR, Yamamoto F, Bobkov AA, Kiselar J, Liu Y, Cadwell GW, Khare S, Yu J, Barquilla A, Chung TD, Mustelin T, Schenk S, Bankston LA, Liddington RC, Pinkerton AB, Bottini N. Diabetes reversal by inhibition of the low-molecular-weight tyrosine phosphatase. Nat Chem Biol. 2017 Mar 27. doi: 10.1038/nchembio.2344. PMID:28346406 doi:http://dx.doi.org/10.1038/nchembio.2344
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