Fig. 1
From: A new paradigm of DNA synthesis: three-metal-ion catalysis
DNA synthesis reaction. a Chemistry of DNA synthesis reaction. b The structure of Pol η-DNA-dNTP (enzyme-substrate) complex (ES) replete with the canonical two metal ions. The B-site metal ion comes along with dNTP. Binding of the A site metal ion is greatly enhanced by a correct incoming dNTP, which forms a Watson–Crick base pair with the template base. With two canonical metal ions bound, the reactants 3′-OH and the α-phosphate of dNTP are perfectly aligned, but without the C-site metal ion no reaction can take place. c DNA Pol η in the enzyme-product complex (EP). The third metal ion occupies the C site and is coordinated by oxygen atoms from product DNA and pyrophosphate. The other four coordination ligands are water molecules, one of which may donate a proton to the pyrophosphate leaving group. d Co-existing ES and EP complexes of DNA Pol η. The third metal ion would clash with dNTP and is incompatible with the ES complex. The largest changes between ES and EP are the scissile phosphorus and the sugar pucker of the 3′-end nucleotide. e Superposition of DNA Pol η (purple Mg2+) and Pol β (pink and green Mn2+) in the enzyme-product complexes (EP). Despite different tertiary structures, the third metal ion (Mn2+) is also found in DNA Pol β in the same coordination geometry as in Pol η