bi050110o_si_001.pdf (37.02 kB)
Inactivation of Bacterial dd-Peptidase by β-Sultams†
journal contribution
posted on 2005-05-31, 00:00 authored by Antonio Llinás, Naveed Ahmed, Massimiliano Cordaro, Andrew P. Laws, Jean-Marie Frère, Michael Delmarcelle, Nicholas R. Silvaggi, Judith A. Kelly, Michael I. PageN-Acyl-β-sultams are time-dependent, irreversible active site-directed inhibitors of Streptomyces
R61 dd-peptidase. The rate of inactivation is first order with respect to β-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 β-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.