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Phosphorus‐containing inhibitors of aspartate transcarbamoylase from Escherichia coli
Author(s) -
Laing Naomi,
Chan William W.-C.,
Hutchinsoi David W.,
Öberg Bo
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)80104-q
Subject(s) - aspartate carbamoyltransferase , pyrophosphate , chemistry , escherichia coli , enzyme , stereochemistry , biochemistry , allosteric regulation , gene
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.