No bend in the DNA is necessary to reach the polymerase active site. The 3' OH of the primer strand interacts with a Mg ion that is bound to a highly conserved aspartic acid residue. Mutations in this residue abolish polymerase activity. A network of hydrogen bonds is made between the sugar-phosphate backbone of the DNA and highly conserved residues of the protein. Two helices forming the thumb region twist so as to widen the polymerase cleft.
Helices forming the fingers region also move to widen the DNA binding cleft by several Angstroms.
The new structures combined with site directed mutagenesis studies suggest several residues that may have a key role in the fidelity of synthesis. The next key experiment for understanding the fidelity of replication is to determine the structure of the polymerase with DNA substrate and nucleotide triphosphates. Much to our surprise the polymerase retained catalytic activity in the crystals. The length of DNA primer increased by one nucleotide. The structures of ternary complexes including correct mismatched nucleotides are now being pursued.