{Reference Type}: Journal Article
{Title}: Third Metal Ion Dictates the Catalytic Activity of the Two-Metal-Ion Pre-Ribosomal RNA-Processing Machinery.
{Author}: Borišek J;Aupič J;Magistrato A;
{Journal}: Angew Chem Int Ed Engl
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jul 12
{Factor}: 16.823
{DOI}: 10.1002/anie.202405819
{Abstract}: Nucleic acid processing enzymes use a two-Mg2+-ion motif to promote the formation and cleavage of phosphodiester bonds. Yet, recent evidence demonstrates the presence of spatially conserved second-shell cations surrounding the catalytic architecture of proteinaceous and RNA-dependent enzymes. The RNase mitochondrial RNA processing (MRP) complex, which cleaves the ribosomal RNA (rRNA) precursor at the A3 cleavage site to yield mature 5'-end of 5.8S rRNA, hosts in the catalytic core one atypically-located Mg2+ ion, in addition to the ions forming the canonical catalytic motif. Here, we employ biased quantum classical molecular dynamics simulations of RNase MRP to discover that the third Mg2+ ion inhibits the catalytic process. Instead, its displacement in favour of a second-shell monovalent K+ ion propels phosphodiester bond cleavage by enabling the formation of a specific hydrogen bonding network that mediates the essential proton transfer step. This study points to a direct involvement of a transient K+ ion in the catalytic cleavage of the phosphodiester bond and implicates cation trafficking as a general mechanism in nucleic acid processing enzymes and ribozymes.