User:Alexsandra Tifane Santos do Nascimento/Sandbox 1
From Proteopedia
Human protein phosphatase 2C
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The human branched-chain α-ketoacid dehydrogenase complex ser/thr phosphatase, PP2Cm, (BDP) is attached to the E2 core through non-covalent bonds. PP2Cm is distinguished from other groups of phosphatases by its structural distinction, absolute requirement for divalent cation, the catalytic domain and shows Mn2+/Mg2+ dependent phosphatase activity. PP2Cm structure has two central antiparallel beta sheets that are flanked by alpha helices and the is located at one end of the beta-sheet sandwich containing two coordenated by residues. At high levels of branched-chain ketoacids PP2Cm dephosphorylates Ser-337 and activates mitochondrial BCKDC complex by associating with the E2 component of the complex. The water molecules at the binuclear metal centre coordinate the phosphate group of the substrate, each ion is hexa-coordinated by from water, providing a nucleophile and general acid in the dephosphorylation reaction, and Arg33 creates a local positive electrostatic potential on the protein for recognition of the phosphate group of the substrate. The nucleophile is the metal-bridging water molecule which could attack the phosphorus atom in an SN2 mechanism. Coordination to two Mg2+ ions may stabilize the morenucleophilic hydroxide ion species. Other ions such as Ca2+, Zn2+ and Ni2+ inactivate the enzyme by competitively inhibiting Mn2+ or Mg2+ binding.
branched-chain α-ketoacid dehydrogenase complex
The human branched-chain α-ketoacid dehydrogenase (BCKD) complex is part of the mitochondrial α-ketoacid dehydrogenase complex family. Their structure consists of numerous copies of three enzymes E1, E2 and E3. A forms the core of the complex with 24 copies in octahedral symmetry. Copies of the , and copies of the. In some types of (BCKDC) that are two regulatory enzymes proteins and that are attached to the E2 core through non-covalent bonds.
References, for further information on PP2Cm
- Ævarsson, A. et all "Crystal structure of human branched-chain α-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease", CellPress. [1].
- Wynn, R. M. et all "Structure, function and assembly of mammalian branched-chain α-ketoacid dehydrogenase complex", Alpha-Keto Acid Dehydrogenase Complexes. [2]
- Lu, G. et all "Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells", The Journal of clinical investigation 119(6):1678-87. [3].
- Pan, B. F et all "Regulation of PP2Cm expression by miRNA-204/211 and miRNA-22 in mouse and human cells [4]