Issue 7, 2014

Zinc ions modulate protein tyrosine phosphatase 1B activity

Abstract

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

Graphical abstract: Zinc ions modulate protein tyrosine phosphatase 1B activity

Supplementary files

Article information

Article type
Paper
Submitted
21 Mar 2014
Accepted
25 Apr 2014
First published
25 Apr 2014
This article is Open Access
Creative Commons BY license

Metallomics, 2014,6, 1229-1239

Author version available

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