The article discusses the mechanisms and structures of protein serine/threonine phosphatases (PSPs), focusing on three major classes: phosphoprotein phosphatases (PPPs), metal-dependent protein phosphatases (PPMs), and aspartate-based phosphatases (ATPs). The text highlights the role of PSPs in various cellular processes and their regulatory mechanisms. Key points include: 1. **PPPs**: These enzymes, exemplified by PP1 and PP2A, achieve substrate specificity through interactions between conserved catalytic subunits and regulatory subunits. The catalytic subunit of PP1 adopts a compact α/β fold, while PP2A consists of a scaffold subunit and a catalytic subunit, both of which interact with regulatory subunits to form holoenzymes. 2. **PPMs**: Members of this family, such as PP2C, contain both catalytic and regulatory domains. They are insensitive to inhibition by certain toxins and play roles in stress signaling and other cellular processes. 3. **ATPs**: FCP/SCP uses an aspartate-based catalysis mechanism and is involved in dephosphorylating the C-terminal domain of RNA polymerase II. The article also delves into the structural and biochemical details of specific PSPs, including PP1, calcineurin (PP2B), PP2A, PP5, and PP2C, providing insights into their substrate recognition, regulation, and catalytic mechanisms. Structural studies have revealed the intricate interactions between subunits and the roles of metal ions in catalysis. Additionally, the text discusses the reversible methylation of PP2A and the autoinhibition mechanisms of PP5, highlighting the complexity and diversity of PSP functions.The article discusses the mechanisms and structures of protein serine/threonine phosphatases (PSPs), focusing on three major classes: phosphoprotein phosphatases (PPPs), metal-dependent protein phosphatases (PPMs), and aspartate-based phosphatases (ATPs). The text highlights the role of PSPs in various cellular processes and their regulatory mechanisms. Key points include: 1. **PPPs**: These enzymes, exemplified by PP1 and PP2A, achieve substrate specificity through interactions between conserved catalytic subunits and regulatory subunits. The catalytic subunit of PP1 adopts a compact α/β fold, while PP2A consists of a scaffold subunit and a catalytic subunit, both of which interact with regulatory subunits to form holoenzymes. 2. **PPMs**: Members of this family, such as PP2C, contain both catalytic and regulatory domains. They are insensitive to inhibition by certain toxins and play roles in stress signaling and other cellular processes. 3. **ATPs**: FCP/SCP uses an aspartate-based catalysis mechanism and is involved in dephosphorylating the C-terminal domain of RNA polymerase II. The article also delves into the structural and biochemical details of specific PSPs, including PP1, calcineurin (PP2B), PP2A, PP5, and PP2C, providing insights into their substrate recognition, regulation, and catalytic mechanisms. Structural studies have revealed the intricate interactions between subunits and the roles of metal ions in catalysis. Additionally, the text discusses the reversible methylation of PP2A and the autoinhibition mechanisms of PP5, highlighting the complexity and diversity of PSP functions.