Phosphorus‐containing inhibitors of aspartate transcarbamoylase from <i>Escherichia coli</i>

A tetrahedral intermediate is the prominent feature of the generally accepted mechanism for aspartate transcarbamoylase. We have synthesized N‐pyrophosphoryl‐L‐aspartate as a charged analogue of the postulated intermediate. Surprisingly, its affinity for the enzyme from Escherichia coli was substantially lower than that of the previously known inhibitor phosphonoacetyl‐L‐aspartate which contained a trigonal carbonyl group. Similar results were obtained with the corresponding mercaptosuccinate derivatives. We also tested a number of new pyrophosphate analogues as inhibitors. Our results cast doubt on some aspects of the current model for the mechanism of this enzyme.

Phosphorus‐containing inhibitors of aspartate transcarbamoylase from Escherichia coli Journal Articles