Structure, dynamics, and molecular inhibition of the Staphylococcus aureus m¹A22-tRNA methyltransferase TrmK.

ABSTRACT: The enzyme m¹A22-tRNA methyltransferase (TrmK) catalyzes the transfer of a methyl group to the N1 of adenine 22 in bacterial tRNAs. TrmK is essential for Staphylococcus aureus survival during infection but has no homolog in mammals, making it a promising target for antibiotic development. Here, we characterize the structure and function of S. aureus TrmK (SaTrmK) using X-ray crystallography, binding assays, and molecular dynamics simulations. We report crystal structures for the SaTrmK apoenzyme as well as in complexes with methyl donor SAM and co-product product SAH. Isothermal titration calorimetry showed that SAM binds to the enzyme with favorable but modest enthalpic and entropic contributions, whereas SAH binding leads to an entropic penalty compensated for by a large favor

SUBMITTER: Sweeney P 

PROVIDER: S-EPMC9190014 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature