Abstract
Peptidoglycan deacetlyase (HP0310, HpPgdA) from the gram-negative pathogen Helicobacter pylori, has been indicated as the enzyme responsible for a peptidoglycan modification that counteracts the host immune response. HpPgdA has been cloned, purified and expressed in good yield in E. coli. It has been crystallized, its structure determined and activity tests in vitro performed. The enzyme, which belongs to the polysaccharide deacetylases protein family, is a homo-tetramer. The four polypeptide chains, each folded into a single domain characterized by a non-canonical TIM-barrel fold, are arranged around a four-fold symmetry axis. The active site, one per monomer, contains a heavy ion coordinated in a way similar to other deacetylases. However, the enzyme showed no in vitro activity on the typical polysaccharide substrates of peptidoglycan deacetylases. In striking contrast with the known peptidoglycan deacetylases, HpPgdA does not exhibit a solvent-accessible polysaccharide binding groove, suggesting that the enzyme binds a small molecule at the active site.
Highlights
Peptidoglycan, which is one of the constituents of the protective barrier of gram-negative bacteria, at the same time represents one of the main targets of the innate immune system of the host [1]
In order to escape the recognition by the host receptors, some bacteria have developed a mechanism of chemical modification of peptidoglycan, in particular through N-deacetylation [1]
In Helicobacter pylori, the gram-negative pathogen that affects about half of the human population, this task is accomplished by a peptidoglycan deactelyase coded by gene hp0310 [4,5]
Summary
Peptidoglycan, which is one of the constituents of the protective barrier of gram-negative bacteria, at the same time represents one of the main targets of the innate immune system of the host [1]. In Helicobacter pylori, the gram-negative pathogen that affects about half of the human population, this task is accomplished by a peptidoglycan deactelyase coded by gene hp0310 [4,5]. It was demonstrated that the HP0310 protein was overexpressed under strong oxidative stress conditions and that peptidoglycan of a HP0310 knock-out mutant presented larger acetylation compared to wild-type, along with increased susceptibility to lysozyme degradation. Expression of HP0310 was induced when H. pylori was held in contact with macrophages and a significant increase of IL-10 and TNF-a was observed in mutant-infected mice compared to wild-type
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