Structure of the phosphocysteine intermediate of the phosphatase of regenerating liver PTP4A1.

ABSTRACT: Phosphatases of regenerating liver (PRL or PTP4A) are protein phosphatases implicated in cell growth, magnesium homeostasis, and cancer metastasis. During catalysis, a phosphocysteine intermediate forms, which must undergo hydrolysis to regenerate the active enzyme. In addition to dephosphorylating substrates, PRLs act as pseudo-phosphatases and bind CBS-pair domain divalent metal cation transport mediators (CNNMs) to regulate magnesium transport. In this study, we investigate the role of PRL residues in phosphocysteine hydrolysis using mutagenesis, enzyme assays, and X-ray crystallography. Loss of an aspartic acid and cysteine in the catalytic site disrupts hydrolysis and stabilizes the phosphocysteine intermediate for weeks. We use this C49S/D72A double mutant to determine the crystal st

SUBMITTER: Mahbub L 

PROVIDER: S-EPMC12192612 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature