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The inactivation of bacterial DD-peptidase by β-sultams

Llinas, Antonio, Ahmed, Naveed, Cordaro, Massimiliano, Laws, Andrew P., Frere, Jean-Marie, Delmarcelle, Michael, Silvaggi, Nicholas R., Kelly, Judith A. and Page, Michael I. (2005) The inactivation of bacterial DD-peptidase by β-sultams. Biochemistry, 44 (21). pp. 7738-7746. ISSN 1520-4995

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N-Acyl--sultams are time-dependent, irreversible active site-directed inhibitors of Streptomyces R61 DD-peptidase. The rate of inactivation is first order with respect to -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 -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

Item Type: Article
Additional Information: Copyright © 2005 American Chemical Society
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Schools: School of Applied Sciences
School of Applied Sciences > Biomolecular Sciences Research Centre
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Date Deposited: 08 Feb 2008 10:57
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