Structure of the catalytic domain of protein tyrosine phosphatase sigma in the sulfenic acid form

Protein tyrosine phosphatase sigma (PTP sigma) plays a vital role in neural development. The extracellular domain of PTP sigma binds to various proteoglycans, which control the activity of 2 intracellular PTP domains (D1 and D2). To understand the regulatory mechanism of PTP sigma, we carried out structural and biochemical analyses of PTP sigma D1D2. In the crystal structure analysis of a mutant form of D1D2 of PTP sigma, we unexpectedly found that the catalytic cysteine of D1 is oxidized to cysteine sulfenic acid, while that of D2 remained in its reduced form, suggesting that D1 is more sensitive to oxidation than D2. This finding contrasts previous observations on PTP alpha. The cysteine sulfenic acid of D1 was further confirmed by immunoblot and mass spectrometric analyses. The stabilization of the cysteine sulfenic acid in the active site of PTP suggests that the formation of cysteine sulfenic acid may function as a stable intermediate during the redox-regulation of PTPs.