An auto-inhibitory helix in CTP:phosphocholine cytidylyltransferase hijacks the catalytic residue and constrains a pliable, domain-bridging helix pair.

ABSTRACT: The activity of CTP:phosphocholine cytidylyltransferase (CCT), a key enzyme in phosphatidylcholine synthesis, is regulated by reversible interactions of a lipid-inducible amphipathic helix (domain M) with membrane phospholipids. When dissociated from membranes, a portion of the M domain functions as an auto-inhibitory (AI) element to suppress catalysis. The AI helix from each subunit binds to a pair of α helices (αE) that extend from the base of the catalytic dimer to create a four-helix bundle. The bound AI helices make intimate contact with loop L2, housing a key catalytic residue, Lys¹²² The impacts of the AI helix on active-site dynamics and positioning of Lys¹²² are unknown. Extensive MD simulations with and without the AI helix revealed that backbone carbonyl ox

SUBMITTER: Ramezanpour M 

PROVIDER: S-EPMC5936808 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature