Article (Scientific journals)
Positive cooperativity between acceptor and donor sites of the peptidoglycan glycosyltransferase.
Bury, Daniel; Dahmane, Ismahene; Derouaux, Adeline et al.
2015In Biochemical Pharmacology, 93 (2), p. 141-50
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Keywords :
Glycosyltransferase; Lipid II; Moenomycin; Peptidoglycan; SPR
Abstract :
[en] The glycosyltransferases of family 51 (GT51) catalyze the polymerization of lipid II to form linear glycan chains, which, after cross linking by the transpeptidases, form the net-like peptidoglycan macromolecule. The essential function of the GT makes it an attractive antimicrobial target; therefore a better understanding of its function and its mechanism of interaction with substrates could help in the design and the development of new antibiotics. In this work, we have used a surface plasmon resonance Biacore((R)) biosensor, based on an amine derivative of moenomycin A immobilized on a sensor chip surface, to investigate the mechanism of binding of substrate analogous inhibitors to the GT. Addition of increasing concentrations of moenomycin A to the Staphylococcus aureus MtgA led to reduced binding of the protein to the sensor chip as expected. Remarkably, in the presence of low concentrations of the most active disaccharide inhibitors, binding of MtgA to immobilized moenomycin A was found to increase; in contrast competition with moenomycin A occurred only at high concentrations. This finding suggests that at low concentrations, the lipid II analogs bind to the acceptor site and induce a cooperative binding of moenomycin A to the donor site. Our results constitute the first indication of the existence of a positive cooperativity between the acceptor and the donor sites of peptidoglycan GTs. In addition, our study indicates that a modification of two residues (L119N and F120S) within the hydrophobic region of MtgA can yield monodisperse forms of the protein with apparently no change in its secondary structure content, but this is at the expense of the enzyme function.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Bury, Daniel
Dahmane, Ismahene ;  Université de Liège - ULiège > Centre d'ingénierie des protéines
Derouaux, Adeline ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Dumbre, Shrinivas
Herdewijn, Piet
Matagne, André  ;  Université de Liège - ULiège > Département des sciences de la vie > Enzymologie et repliement des protéines
Breukink, Eefjan
Mueller-Seitz, Erika
Petz, Michael
Terrak, Mohammed  ;  Université de Liège - ULiège > Centre d'ingénierie des protéines
Language :
English
Title :
Positive cooperativity between acceptor and donor sites of the peptidoglycan glycosyltransferase.
Publication date :
2015
Journal title :
Biochemical Pharmacology
ISSN :
0006-2952
eISSN :
1873-2968
Publisher :
Elsevier, Netherlands
Volume :
93
Issue :
2
Pages :
141-50
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2014 Elsevier Inc. All rights reserved.
Available on ORBi :
since 05 February 2015

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