Reference : Structural basis of the inhibition of class A beta-lactamases and penicillin-binding pro...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/34153
Structural basis of the inhibition of class A beta-lactamases and penicillin-binding proteins by 6-beta-iodopenicillanate
English
Sauvage, Eric mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Zervosen, Astrid mailto [Université de Liège - ULg > > Centre de recherches du cyclotron >]
Dive, Georges mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Herman, Raphaël mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Amoroso, Ana Maria mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Joris, Bernard mailto [Université de Liège - ULg > Département des sciences de la vie > Physiologie et génétique bactériennes - Centre d'ingénierie des protéines >]
Fonzé, Eveline [> >]
Pratt, Rex [> >]
Luxen, André mailto [Université de Liège - ULg > Département de chimie (sciences) > Chimie organique de synthèse - Centre de recherches du cyclotron >]
Charlier, Paulette mailto [Université de Liège - ULg > Département des sciences de la vie > Cristallographie des macromolécules biologiques >]
Kerff, Frédéric mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
2009
Journal of the American Chemical Society
American Chemical Society
131
42
15262-15269
Yes (verified by ORBi)
International
0002-7863
1520-5126
Washington
DC
[en] 6-Beta-halogenopenicillanates are powerful, irreversible inhibitors of various beta-lactamases and penicillin-binding proteins. Upon acylation of these enzymes, the inhibitors are thought to undergo a structural rearrangement associated with the departure of the iodide and formation of a dihydrothiazine ring, but, to date, no structural evidence has proven this. 6-Beta-iodopenicillanic acid (BIP) is shown here to be an active antibiotic against various bacterial strains and an effective inhibitor of the class A beta-lactamase of Bacillus subtilis BS3 (BS3) and the D,D-peptidase of Actinomadura R39 (R39). Crystals of BS3 and of R39 were soaked with a solution of BIP and their structures solved at 1.65 and 2.2 A, respectively. The beta-lactam and the thiazolidine rings of BIP are indeed found to be fused into a dihydrothiazine ring that can adopt two stable conformations at these active sites. The rearranged BIP is observed in one conformation in the BS3 active site and in two monomers of the asymmetric unit of R39, and is observed in the other conformation in the other two monomers of the asymmetric unit of R39. The BS3 structure reveals a new mode of carboxylate interaction with a class A beta-lactamase active site that should be of interest in future inhibitor design.
Researchers ; Professionals
http://hdl.handle.net/2268/34153
also: http://hdl.handle.net/2268/31163
10.1021/ja9051526

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Open access
jacs_2009_131_15262_eric.pdfNo commentaryPublisher postprint3.18 MBView/Open

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.