Zinc ions modulate protein tyrosine phosphatase 1B activity

• DOI: 10.1039/c4mt00086b
• Publication Date: 2014-04-25T11:01:19Z
• Authors: Elisa Bellomo; Alberto Massarotti; Christer Hogstrand; Wolfgang Maret
• Keywords: Protein Tyrosine Phosphatase, Non-Receptor Type 1; 0301 basic medicine; 570; 0303 health sciences; Binding Sites; 572; 16. Peace & justice; Receptor, Insulin; Molecular Docking Simulation; Zinc; 03 medical and health sciences; Humans; Receptors, Leptin; Enzyme Inhibitors; Edetic Acid

Protein tyrosine phosphatases (PTPs) are key enzymes in cellular regulation. The 107 human PTPs regulated by redox signalling, phosphorylation, dimerisation, and proteolysis. Recent findings of very strong inhibition some zinc ions at concentrations relevant a environment suggest yet another mechanism One the most extensively investigated is PTP1B (PTPN1). It regulates insulin leptin signalling pathway implicated cancer obesity/diabetes. development novel assay conditions to investigate provides estimates about 5.6 nM affinity for inhibitory zinc(II) ions. Analysis three 3D structures (PDB id: 2CM2, 3I80 1A5Y) identified putative binding sites supports kinetic studies suggesting an only closed cysteinyl-phosphate intermediate forms enzyme. These observations gain significance with regard recent regulatory roles released from endoplasmic reticulum.