Mg²⁺-Dependent Methyl Transfer by a Knotted Protein: A Molecular Dynamics Simulation and Quantum Mechanics Study.

ABSTRACT: Mg²⁺ is required for the catalytic activity of TrmD, a bacteria-specific methyltransferase that is made up of a protein topological knot-fold, to synthesize methylated m¹G37-tRNA to support life. However, neither the location of Mg²⁺ in the structure of TrmD nor its role in the catalytic mechanism is known. Using molecular dynamics (MD) simulations, we identify a plausible Mg²⁺ binding pocket within the active site of the enzyme, wherein the ion is coordinated by two aspartates and a glutamate. In this position, Mg²⁺ additionally interacts with the carboxylate of a methyl donor cofactor S-adenosylmethionine (SAM). The computational results are validated by experimental mutation studies, which demonstrate the importance of the Mg²⁺

SUBMITTER: Perlinska AP 

PROVIDER: S-EPMC7462349 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature