DNA polymerases change their specificity for nucleotide substrates wit
h each catalytic cycle, while achieving error frequencies in the range
of 10(-5) to 10(-6). Here we present a 2.2 Angstrom crystal structure
of the replicative DNA polymerase from bacteriophage T7 complexed wit
h a primer-template and a nucleoside triphosphate in the polymerase ac
tive site. The structure illustrates how nucleotides are selected in a
template-directed manner, and provides a structural basis for a metal
-assisted mechanism of phosphoryl transfer by a large group of related
polymerases.