北医本科课件《生物化学》2009 Cell Serine threonine phosphatases mechanism through structure by Shi Y.pdfVIP

Leading Edge Review Serine/Threonine Phosphatases: Mechanism through Structure 1, Yigong Shi * 1Center for Structural Biology, School of Life Sciences, and School of Medicine, Tsinghua University, Beijing 100084, China *Correspondence: shi-lab@ DOI 10.1016/j.cell.2009.10.006 The reversible phosphorylation of proteins is accomplished by opposing activities of kinases and phosphatases. Relatively few protein serine/threonine phosphatases (PSPs) control the specific dephosphorylation of thousands of phosphoprotein substrates. Many PSPs, exemplified by protein phosphatase 1 (PP1) and PP2A, achieve substrate specificity and regulation through combinato- rial interactions between conserved catalytic subunits and a large number of regulatory subunits. Other PSPs, represented by PP2C and FCP/SCP, contain both catalytic and regulatory domains within the same polypeptide chain. Here, we discuss biochemical and structural investigations that advance the mechanistic understanding of the three major classes of PSPs, with a focus on PP2A. The concept of protein phosphorylation, discovered by et al., 2001; Venter et al., 2001) that can be classified into Edmond Fischer and Edwin Krebs, arose from the dem- two families: 90 tyrosine (Tyr) kinases (PTKs) and 428 serine/ onstration of a dual requirement for ATP and a “converting threonine (Ser/Thr) kinases (PSKs). The exquisite specific- enzyme” (subsequently named phosphorylase kinase) in the ity of signaling and the reversible nature of phosphorylation in vitro conversion of phosphorylase b to phosphorylase a seem to suggest that there would be similar