Reference : The active centres in penicillin-sensitive enzymes
Scientific journals : Article
Life sciences : Microbiology
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/91671
The active centres in penicillin-sensitive enzymes
English
Ghuysen, Jean-Marie [Université de Liège - ULiège > Institut de Botanique > Service de Microbiologie > >]
Frère, Jean-Marie mailto [Université de Liège - ULiège > Institut de Botanique > Service de Microbiologie > > > >]
Leyh-Bouille, Mélina [Université de Liège - ULiège > Institut de Botanique > Service de Microbiologie > > > >]
Perkins, H.-R. [University of Liverpool > Life Sciences > Department of Microbiology > >]
Nieto, Manuel [Instituto de Biologica Celular > Centro de Investigationes Biologicas > > >]
16-May-1980
Philosophical Transactions : Biological Sciences
Royal Society of London
289
1036
285-301
Yes (verified by ORBi)
International
0962-8436
1471-2970
London
United Kingdom
[en] amino acid sequence ; binding sites ; cephalosporins/metabolism ; enzymes/*metabolism ; models, chemical ; penicillins/*pharmacology
[en] The interaction between beta-lactam antibiotics and the penicillin-sensitive enzymes is a multiple-step process. Binding of the beta-lactam ring of the penam (or 3-cepham) nucleus occurs at binding site no. 1. Interaction between the N-14 substituent of the bound molecule and binding site no. 2 induces changes in binding site no. 1. In turn, the catalytic site thus created increases the chemical reactivity of the beta-lactam amide bond. As the beta-lactam ring opens and acylates an enzyme serine residue, the interaction between the thiazolidine (or dihydrothiazine) ring and binding site no. 3 stabilizes the acyl-enzyme complex. Enzyme regeneration slowly proceeds either by direct elimination of the penicilloyl moiety or via C-5-C-6 splitting of the bound metabolite. The fragment arising from thiazolidine yields free N-formyl-D-penicillamine while the enzyme-linked N-acylglycyl fragment is immediately attacked by an exogenous nucleophile correctly positioned on the acceptor site. Similarly, the enzyme action on L-X-D-Ala-D-Ala terminated peptides is mediated via a binding site no. 1 that combines with D-Ala-D-Ala, a binding site no. 2 that interacts with the side chain of the preceding L-residue, an inducible catalytic site and an acceptor site. Enzymes are known that form a transitory L-X-D-Ala-enzyme complex where the acyl group is ester-linked to the same serine residue as that involved in the formation of the penicilloyl-enzyme complex (Waxman et al., this symposium). Other enzymes, however, may function as catalyst templates. Depending on the enzymes, the independence of the beta-lactam and L-X-D-Ala-D-Ala active centres is more or less pronounced.
National Institutes of Health - NIH
Researchers ; Professionals ; Students ; General public ; Others
http://hdl.handle.net/2268/91671

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