5jnv

Crystal structure of bovine low molecular weight protein tyrosine phosphatase (LMPTP) mutant (W49Y N50E) complexed with HEPES

spinqualitylabelsall models 5jnv, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5jnv is a 1 chain structure with sequence from Bovin. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DMS, EPE Related: 5jnr, 5jns, 5jnt, 5jnu, 5jnw Gene: ACP1 (BOVIN) Activity: Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PPAC_BOVIN] Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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