Transition-State Analysis for Depurination of DNA by Ricin A-Chain

Ricin toxin A-chain (RTA) exerts its cytotoxicity by depurinating 28 S ribosomal RNA at ribonucleotide A4234, a site of eukaryotic elongation factor binding. Small stem-loop RNAs and DNAs can also be depurinated at the first adenine residue of 5‘-GAGA-3‘ tetraloops. DNA oligonucleotides were synthesized with DNA polymerase, using dATP labeled with [1‘-14C], [5‘-14C,9-15N], [1‘-3H], [2‘R-3H], [2‘S-3H] or [5‘-3H]. Kinetic isotope effects (KIEs) …