Molecular Dynamics Simulation Studies of dTTP Binding and Catalysis Mediated by YhdE Dimerization.

摘要: YhdE is a Maf-like (multicopy associated filamentation) protein that primarily acts as dTTPase to hydrolyze dTTP into dTMP and two phosphate molecules in cell metabolism pathway. Two crystal structures of have been previously determined, representing the open closed active site conformations, respectively. Based on structures, we carried out molecular dynamics simulations free energy calculations investigate binding hydrolysis by YhdE. Our results suggest state structurally more compact than its at room temperature. favorable conformation for catalytic reaction. This observation supported structure homolog complex with nucleotide analog. Free reveal dimerization occurs preferentially successive cooperative The key residues R11, R12 K80, are found contribute substrate stabilization. Further, induce effect through direct allosteric communication network from sites center intermolecular β-strand dimer.