How does the nucleophilic attack in DNA replication occur?
Polymerases uses a two-metal ion mechanism to carry out the addition of a new NTP to a growing RNA strand. Two Mg2+ ions are used in this process; metal ion A is involved in the formation of the nucleophile (O-) for the SN2 reaction to occur and metal ion B is involved in the stabilization of the transition state in the reaction. For the addition of a NTP to a RNA strand to occur, an activated 3’ hydroxyl group (O-) acts a nucleophile and attacks the alpha phosphate of the incoming NTP. The reaction is initiated by a deprotonation event. Metal ion A aids with this deprotonation as it reduces the pKa of the hydroxyl (so it is more acidic), making it easier to deprotonate and form the nucleophile, the proton is accepted by a nearby aspartate residue (not water) - doi: 10.1021/ja403842j. After the hydroxyl attack, the mechanism proceeds through a pentacovalent transition state like in a standard Sn2 reaction and the pyrophosphate group (PPi) is kicked out. The image is not mine but comes from this paper: https://doi.org/10.1038/34542, which is quite good, as is this paper: doi: 10.1074/jbc.274.25.17395 and this one https://doi.org/10.1016/j.molcel.2006.03.013