Crystal structures and snapshots along Tpt1-catalyzed phosphate transfer from nucleic acid to NAD^.

ABSTRACT: Tpt1/TRPT1/KptA family proteins are evolutionarily conserved in all three domains of life. In fungi and plants, Tpt1 transfers 2'-PO₄^2- from tRNA splice junction to NAD⁺, which is the final step of tRNA maturation and is critical for the function of tRNA. In mammals and bacteria, Tpt1-catalyzed reaction leads to 5'-end ADP ribosylation, a reversible chemical modification of nucleic acids. Based on in vivo and in vitro biochemical studies, a two-step catalytic mechanism has been established for Tpt1-catalyzed RNA 2'-PO₄^2- transfer, including (i) the 2'-PO₄^2- attacks NAD⁺, releasing nicotinamide and forming a 2'-phospho-ADP-ribosylated RNA (2'-p-ADPR-RNA) intermediate; and (ii) transesterification of the

SUBMITTER: Cao C 

PROVIDER: S-EPMC12678800 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature