4rag | pdb_00004rag

CRYSTAL STRUCTURE of PPC2A-D38K

spinqualitylabelsall models 4rag, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4rag is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MN Related: 4ra2, 4raf Gene: PPM1A, PPPM1A (HUMAN) Activity: Phosphoprotein phosphatase, with EC number 3.1.3.16 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PPM1A_HUMAN] Enzyme with a broad specificity. Negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling. Publication Abstract from PubMed PP2C family phosphatases (the type 2C family of protein phosphatases; or metal-dependent phosphatase, PPM) constitute an important class of signaling enzymes that regulate many fundamental life activities. All PP2C family members have a conserved binuclear metal ion active center that is essential for their catalysis. However, the catalytic role of each metal ion during catalysis remains elusive. In this study, we discovered that mutations in the structurally buried D38 residue of PP2Calpha (PPM1A) redefined the water-mediated hydrogen network in the active site and selectively disrupted M2 metal ion binding. Using the D38A and D38K mutations of PP2Calpha as specific tools in combination with enzymology analysis, our results demonstrated that the M2 metal ion determines the rate-limiting step of substrate hydrolysis, participates in dianion substrate binding and stabilizes the leaving group after P-O bond cleavage. The newly characterized catalytic role of the M2 metal ion in this family not only provides insight into how the binuclear metal centers of the PP2C phosphatases are organized for efficient catalysis but also helps increase our understanding of the function and substrate specificity of PP2C family members. The catalytic role of the M2 metal ion in PP2Calpha.,Pan C, Tang JY, Xu YF, Xiao P, Liu HD, Wang HA, Wang WB, Meng FG, Yu X, Sun JP Sci Rep. 2015 Feb 24;5:8560. doi: 10.1038/srep08560. PMID:25708299 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Protein phosphatase

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