Two-metal versus one-metal mechanisms of lysine adenylylation by ATP-dependent and NAD⁺-dependent polynucleotide ligases.

ABSTRACT: Polynucleotide ligases comprise a ubiquitous superfamily of nucleic acid repair enzymes that join 3'-OH and 5'-PO₄ DNA or RNA ends. Ligases react with ATP or NAD⁺ and a divalent cation cofactor to form a covalent enzyme-(lysine-Nζ)-adenylate intermediate. Here, we report crystal structures of the founding members of the ATP-dependent RNA ligase family (T4 RNA ligase 1; Rnl1) and the NAD⁺-dependent DNA ligase family (Escherichia coli LigA), captured as their respective Michaelis complexes, which illuminate distinctive catalytic mechanisms of the lysine adenylylation reaction. The 2.2-Å Rnl1•ATP•(Mg²⁺)₂ structure highlights a two-metal mechanism, whereby: a ligase-bound "catalytic" Mg²⁺(H₂O)₅ coord

SUBMITTER: Unciuleac MC 

PROVIDER: S-EPMC5347617 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature