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

ABSTRACT: Protein tyrosine phosphatase sigma (PTP?) plays a vital role in neural development. The extracellular domain of PTP? binds to various proteoglycans, which control the activity of 2 intracellular PTP domains (D1 and D2). To understand the regulatory mechanism of PTP?, we carried out structural and biochemical analyses of PTP? D1D2. In the crystal structure analysis of a mutant form of D1D2 of PTP?, 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?. 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.

SUBMITTER: Jeon TJ 

PROVIDER: S-EPMC3887927 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature