[en] N-Acyl-beta-sultams are time-dependent, irreversible active site-directed inhibitors of Streptomyces R61 DD-peptidase. The rate of inactivation is first order with respect to beta-sultam concentration, and the second-order rate constants show a dependence on pH similar to that for the hydrolysis of a substrate. Inactivation is due to the formation of a stable 1:1 enzyme-inhibitor complex as a result of the active site serine being sulfonylated by the beta-sultam as shown by ESI-MS analysis and by X-ray crystallography. A striking feature of the sulfonyl enzyme is that the inhibitor is not bound to the oxyanion hole but interacts extensively with the "roof" of the active site where the Arg 285 is located.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Llinas, Antonio
Ahmed, Naveed
Cordaro, Massimiliano
Laws, Andrew P
Frère, Jean-Marie ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Delmarcelle, Michaël ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Silvaggi, Nicholas R
Kelly, Judith A
Page, Michael I
Language :
English
Title :
Inactivation of bacterial DD-peptidase by beta-sultams.
Publication date :
2005
Journal title :
Biochemistry
ISSN :
0006-2960
eISSN :
1520-4995
Publisher :
American Chemical Society, Washington, United States - District of Columbia
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
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