PHP domain metal-coordinating residues are not conserved. (A) Sequence alignment of C-family DNA polymerase PHP domains. The figure shows a selected set of sequences from our larger (47-sequence) alignment. Only sequences of polymerases that have been structurally or biochemically characterized were selected. For each polymerase the GI number and subtype within the C-family is indicated. For the conservation score diagram, the height of the bars is proportional to the conservation of the residues in our large alignment of C-family DNA polymerase sequences, as determined according to . Black arrows at the top indicate the positions of variation in E. coli. (B) PHP domain cleft of C-family DNA polymerases. Metal-binding residues (or their substitutes in mutated PHP domains) are shown in ball and stick representation. Phosphate ions in E. coli Pol III and G. kaustophilus Pol C have been omitted for clarity.