|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5jnu' size='340' side='right'caption='[[5jnu]], [[Resolution|resolution]] 2.54Å' scene=''> | | <StructureSection load='5jnu' size='340' side='right'caption='[[5jnu]], [[Resolution|resolution]] 2.54Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jnu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JNU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JNU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jnu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JNU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JNU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.535Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jnr|5jnr]], [[5jns|5jns]], [[5jnt|5jnt]], [[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=PO4:PHOSPHATE+ION'>PO4</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=10090 LK3 transgenic mice])</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=5jnu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jnu OCA], [https://pdbe.org/5jnu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jnu RCSB], [https://www.ebi.ac.uk/pdbsum/5jnu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jnu 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=5jnu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jnu OCA], [http://pdbe.org/5jnu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jnu RCSB], [http://www.ebi.ac.uk/pdbsum/5jnu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jnu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PPAC_MOUSE PPAC_MOUSE]] Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates.[UniProtKB:P11064] | + | [https://www.uniprot.org/uniprot/PPAC_MOUSE PPAC_MOUSE] Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates.[UniProtKB:P11064] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 26: |
Line 24: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[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_MOUSE Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates.[UniProtKB:P11064]
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
|
