Phosphorus‐containing inhibitors of aspartate transcarbamoylase from Escherichia coli

FEBS Letters

Öberg, Bo²  Hutchinsoi, David W.¹  Chan, William W.-C.³  Laing, Naomi³ 

[1] Department of Chemistry, University of Warwick, Coventry CV4 7AL, England;Medivir AB, Björnnäsvägen 27, S-11347 Stockholm, Sweden;Department of Biochemistry, McMaster University Medical Centre, Hamilton, Ontario, L8N 3Z5 Canada

关键词: Enzyme inhibition;    Transition state;    N-Pyrophosphoryl-L-aspartate;    Aspartate transcarbamoylase;    (Escherichia coli);    ATCase;    aspartate transcarbamoylase;    PALA;    n-phosphonoacetyl-L-aspartate;   

DOI  :  10.1016/0014-5793(90)80104-Q

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown