Reference : Inactivation of bacterial DD-peptidase by beta-sultams.
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/101012
Inactivation of bacterial DD-peptidase by beta-sultams.
English
Llinas, Antonio [> > > >]
Ahmed, Naveed [> > > >]
Cordaro, Massimiliano [> > > >]
Laws, Andrew P [> > > >]
Frère, Jean-Marie mailto [Université de Liège - ULiège > > Centre d'ingénierie des protéines >]
Delmarcelle, Michaël mailto [Université de Liège - ULiège > > Centre d'ingénierie des protéines >]
Silvaggi, Nicholas R [> > > >]
Kelly, Judith A [> > > >]
Page, Michael I [> > > >]
2005
Biochemistry
American Chemical Society
44
21
7738-46
Yes (verified by ORBi)
International
0006-2960
1520-4995
Washington
DC
[en] Anti-Bacterial Agents/chemistry ; Bacterial Proteins/antagonists & inhibitors/metabolism ; Binding Sites ; Catalysis ; Crystallography, X-Ray ; Enzyme Inhibitors/chemistry ; Enzyme Reactivators/chemistry ; Enzyme Stability ; Esters ; Hydrogen-Ion Concentration ; Hydrolysis ; Hydroxylamine/chemistry ; Serine/chemistry ; Serine-Type D-Ala-D-Ala Carboxypeptidase/antagonists & inhibitors/metabolism ; Spectrometry, Mass, Electrospray Ionization ; Streptomyces/enzymology/growth & development ; Substrate Specificity ; Sulfhydryl Compounds/chemistry/metabolism ; Sulfonamides/chemistry
[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.
http://hdl.handle.net/2268/101012
10.1021/bi050110o

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