4mvc

Crystal Structure of a Mammalian Cytidylyltransferase

spinqualitylabelsall models 4mvc, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4mvc is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3Å Ligands: CDC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PCY1A_RAT Controls phosphatidylcholine synthesis. Publication Abstract from PubMed CTP:phosphocholine cytidylyltransferase (CCT) interconverts between an inactive soluble and active membrane-bound form in response to changes in membrane lipid composition. Activation involves disruption of an inhibitory interaction between the alphaE helices at the base of the active site and an autoinhibitory (AI) segment in the regulatory M domain and membrane insertion of the M domain as an amphipathic helix. We show that in the CCT soluble form the AI segment functions to suppress kcat and elevate the Km for CTP. The crystal structure of a CCT dimer composed of the catalytic and AI segments reveals an AI-alphaE interaction as a cluster of four amphipathic helices (two alphaE and two AI helices) at the base of the active sites. This interaction corroborates mutagenesis implicating multiple hydrophobic residues within the AI segment that contribute to its silencing function. The AI-alphaE interaction directs the turn at the C-terminal end of the AI helix into backbone-to-backbone contact with a loop (L2) at the opening to the active site, which houses the key catalytic residue, lysine 122. Molecular dynamics simulations suggest that lysine 122 side-chain orientations are constrained by contacts with the AI helix-turn, which could obstruct its engagement with substrates. This work deciphers how the CCT regulatory amphipathic helix functions as a silencing device. Structural Basis for Autoinhibition of CTP:Phosphocholine Cytidylyltransferase (CCT), the Regulatory Enzyme in Phosphatidylcholine Synthesis, by Its Membrane-binding Amphipathic Helix.,Lee J, Taneva SG, Holland BW, Tieleman DP, Cornell RB J Biol Chem. 2014 Jan 17;289(3):1742-55. doi: 10.1074/jbc.M113.526970. Epub 2013 , Nov 25. PMID:24275660 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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