A and the neighbor A118 phosphate pro-R p (O R ) would in contrast be better arranged for deprotonation by the phosphate backbone. Both deprotonation routes could also take place from conformations with increased distances between the base and scissile phosphate ("A118_2wat" and "Glu96_2wat" in Figure ), with indirect proton transfer through an additional water molecule (Figure ). A final possible mechanistic route is the attack of a non-deprotonated water molecule, with proton shuttling towards the leaving group through the scissile A117 phosphate. This proton shuttling can also involve a string of several water molecules, as suggested in RNase H. The different possible reaction mechanisms are depicted in Figure and Figure .