The molecular details of the nucleotidyl transferase reaction have remained speculative, as strategies to trap catalytic intermediates for structure determination utilize substrates lacking the primer terminus 3'-OH and catalytic Mg 2+ resulting in an incomplete and distorted active site geometry. Since the geometric arrangement of these essential atoms will impact chemistry, structural insight into fidelity strategies has been hampered. Here we present the first crystal structure of a pre-catalytic complex of a DNA polymerase with bound substrates that include the primer 3'-OH and catalytic Mg 2+. This catalytic intermediate was trapped with a non-hydrolyzable deoxynucleotide analogue. Comparison with two new structures of DNA polymerase β lacking the 3'-OH or catalytic Mg 2+ is described. These structures provide direct evidence that both atoms are required to achieve a proper geometry necessary for an in-line nucleophilic attack of O3' on the αP of the incoming nucleotide.

The structure of estrogen sulphotransferase has been solved in the presence of inactive cofactor PAP and substrate 17 beta-estradiol. This structure reveals structural similarities between cytosolic sulphotransferases and nucleotide kinases.

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