Bifunctional Penicillin-Binding Proteins: Focus on the Glycosyltransferase Domain and its Specific Inhibitor Moenomycin

Authors: Di Guilmi A.Marie; Dessen A.; Dideberg O.; Vernet T.

Source: Current Pharmaceutical Biotechnology, Volume 3, Number 2, June 2002 , pp. 63-75(13)

Publisher: Bentham Science Publishers

Abstract:

-lactams and glycopeptides antibiotics directed against enzymes involved in bacterial cell wall synthesis have generated bacterial resistance. Search for new antibiotic molecules is widely focused on bifunctional Penicillin-Binding Proteins (PBPs), with particular emphasis on their glycosyltransferase activity. This function catalyzes glycan chain polymerization of the cell wall peptidoglycan. This review summarizes recent results about biochemical characterization of bifunctional PBPs and enzymatic properties of the glycosyltransferase domain. Moenomycin, a well studied glycosyltransferase activity inhibitor has provided useful informations about lipid binding properties and about cellular role of bifunctional PBPs. These enzymes were shown to be a part of the multienzymatic complex involved in peptidoglycan biosynthesis. Furthermore, bifunctional PBPs are also present in the protein complex located at the site of septation during cell division. The glycosyltransferase domain of bifunctional PBPs remains unsufficently characterized: the structural analysis may lead to the development of novel antibacterials and to the understanding of the enzymatic properties, while genetic and cellular studies focused on bifunctional PBPs will provide a wealth of knowledge regarding cell growth and division.

Keywords: pbps; moenomycin; giycosyltransferase

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389201023378436

Publication date: 2002-06-01

• Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in both pre-clinical and clinical areas of Pharmaceutical Biotechnology. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.

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• By this author: Di Guilmi A.Marie ;  Dessen A. ;  Dideberg O. ;  Vernet T.

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