[en] beta-Lactamase and penicillin-binding protein PBP2' mediate staphylococcal resistance to beta-lactam antibiotics, which are otherwise highly clinically effective. Two repressors (BlaI and MecI) regulate expression of these inducible proteins. Here, we present the first solution structure of the 82 amino acid residue DNA-binding domain of Bacillus licheniformis BlaI which is very similar in primary sequence to the medically significant Staphyloccocal BlaI and MecI proteins. This structure is composed of a compact core of three alpha-helices and a three-stranded beta-sheet typical of the winged helix protein (WHP) family. The protein/DNA complex was studied by NMR chemical shift comparison between the free and complexed forms of BlaI. Residues involved in DNA interaction were identified and a WHP canonical model of interaction with the operators is proposed. In this model, specific contacts occur between the base-pairs of the TACA motif and conserved amino acid residues of the repressor helix H3. These results help toward understanding the repression and induction mechanism of the genes coding for beta-lactamase and PBP2'.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Melckebeke, Helene Van
Vreuls, Christelle ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Gans, Pierre
Filée, Patrice ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Llabres, Gabriel ; Université de Liège - ULiège > Département de physique > Département de physique
Joris, Bernard ; Université de Liège - ULiège > Département des sciences de la vie > Physiologie et génétique bactériennes
Simorre, Jean*-Pierre
Language :
English
Title :
Solution structural study of BlaI: implications for the repression of genes involved in beta-lactam antibiotic resistance.
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