Abstract
THE crystal structures of three amidohydrolases have been determined recently1–3: glutamine PRPP amidotransferase (GAT), penicillin acylase, and the proteasome. These enzymes use the side chain of the amino-terminal residue, incorporated in a β-sheet, as the nucleophile in the catalytic attack at the carbonyl carbon. The nucleophile is cysteine in GAT, serine in penicillin acylase, and threonine in the proteasome. Here we show that all three enzymes share an unusual fold in which the nucleophile and other catalytic groups occupy equivalent sites. This fold provides both the capacity for nucleophilic attack and the possibility of autocatalytic processing. We suggest the name Ntn (N-terminal nucleophile) hydrolases for this structural superfamily of enzymes which appear to be evolutionarily related but which have diverged beyond any recog-nizable sequence similarity.
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Brannigan, J., Dodson, G., Duggleby, H. et al. A protein catalytic framework with an N-terminal nucleophile is capable of self-activation. Nature 378, 416–419 (1995). https://doi.org/10.1038/378416a0
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DOI: https://doi.org/10.1038/378416a0
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