4da1

Crystal structure of branched-chain alpha-ketoacid dehydrogenase phosphatase with Mg (II) ions at the active site

spinqualitylabelsall models 4da1, resolution 2.38Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4da1 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: BME, MG Related: 2iq1 Gene: PPM1K, PP2CM (HUMAN) Activity: Phosphoprotein phosphatase, with EC number 3.1.3.16 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [PPM1K_HUMAN] Intermediate maple syrup urine disease. Function [PPM1K_HUMAN] Regulates the mitochondrial permeability transition pore and is essential for cellular survival and development. Publication Abstract from PubMed The branched-chain alpha-ketoacid dehydrogenase phosphatase (BDP) component of the human branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) has been expressed in Escherichia coli and purified in the soluble form. The monomeric BDP shows a strict dependence on Mn(2+) ions for phosphatase activity, whereas Mg(2+) and Ca(2+) ions do not support catalysis. Metal binding constants for BDP, determined by competition isothermal titration calorimetry, are 2.4 nm and 10 mum for Mn(2+) and Mg(2+) ions, respectively. Using the phosphorylated decarboxylase component (p-E1b) of BCKDC as a substrate, BDP shows a specific activity of 68 nmol/min/mg. The Ca(2+)-independent binding of BDP to the 24-meric transacylase (dihydrolipoyl transacylase; E2b) core of BCKDC results in a 3-fold increase in the dephosphorylation rate of p-E1b. However, the lipoyl prosthetic group on E2b is not essential for BDP binding or E2b-stimulated phosphatase activity. Acidic residues in the C-terminal linker of the E2b lipoyl domain are essential for the interaction between BDP and E2b. The BDP structure was determined by x-ray crystallography to 2.4 A resolution. The BDP structure is dominated by a central beta-sandwich. There are two protrusions forming a narrow cleft approximately 10 A wide, which constitutes the active site. The carboxylate moieties of acidic residues Asp-109, Asp-207, Asp-298, and Asp-337 in the active-site cleft participate in binding two metal ions. Substitutions of these residues with alanine nullify BDP phosphatase activity. Alteration of the nearby Arg-104 increases the K(m) for p-E1b peptide by 60-fold, suggesting that this residue is critical for the recognition of the native p-E1b protein. Structural and biochemical characterization of human mitochondrial branched-chain alpha-ketoacid dehydrogenase phosphatase.,Wynn RM, Li J, Brautigam CA, Chuang JL, Chuang DT J Biol Chem. 2012 Mar 16;287(12):9178-92. Epub 2012 Jan 30. PMID:22291014 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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