Specificity of L,D-Transpeptidases from Gram-positive Bacteria Producing Different Peptidoglycan Chemotypes

Magnet, Sophie; Arbeloa, Ana; Mainardi, Jean–Luc; Hugonnet, Jean-Emmanuel; Fourgeaud, Martine; Dubost, Lionel; Marie, Arul; Delfosse, V.; Mayer, Claudine; Rice, Louis B.; Arthur, Michel

doi:10.1074/jbc.m610911200

Cited by 81 publications

(79 citation statements)

References 37 publications

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“…This proposal is consistent with the finding that the LD-transpeptidase from Enterococcus faecalis, which catalyzes the formation of dimers by the removal of D-alanyl-D-alanine from the branched disaccharide-heptapeptide monomer muropeptide, also displays LD-endopeptidase activity catalyzing the removal of D-alanyl-D-alanine from the same substrate (158).…”

Section: Penicillin-insensitive Peptidasessupporting

confidence: 91%

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Peptidoglycan Hydrolases of Escherichia coli

Heijenoort

2011

Microbiol Mol Biol Rev

187

233

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SUMMARY The review summarizes the abundant information on the 35 identified peptidoglycan (PG) hydrolases of Escherichia coli classified into 12 distinct families, including mainly glycosidases, peptidases, and amidases. An attempt is also made to critically assess their functions in PG maturation, turnover, elongation, septation, and recycling as well as in cell autolysis. There is at least one hydrolytic activity for each bond linking PG components, and most hydrolase genes were identified. Few hydrolases appear to be individually essential. The crystal structures and reaction mechanisms of certain hydrolases having defined functions were investigated. However, our knowledge of the biochemical properties of most hydrolases still remains fragmentary, and that of their cellular functions remains elusive. Owing to redundancy, PG hydrolases far outnumber the enzymes of PG biosynthesis. The presence of the two sets of enzymes acting on the PG bonds raises the question of their functional correlations. It is difficult to understand why E. coli keeps such a large set of PG hydrolases. The subtle differences in substrate specificities between the isoenzymes of each family certainly reflect a variety of as-yet-unidentified physiological functions. Their study will be a far more difficult challenge than that of the steps of the PG biosynthesis pathway.

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Section: Penicillin-insensitive Peptidasessupporting

confidence: 91%

“…Biochemical data con- (42) could be a factor limiting its use. An enzyme showing both LD-transpeptidase and LD-carboxypeptidase activities was reported previously for E. faecalis (158).…”

Section: Tripeptide Subunitssupporting

confidence: 70%

Peptidoglycan Hydrolases of Escherichia coli

Heijenoort

2011

Microbiol Mol Biol Rev

187

233

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“…Next, to further strengthen the PG, a transpeptidase reaction occurs that links the DAP of the acceptor peptide to either a DAP or the penultimate D-alanine on the donor peptide. The transpeptidase that forms the DAP-DAP linkage is likely resistant to ␤-lactams and thus represents a potential new drug target (152,253). Unfortunately, the enzyme thought to catalyze this reaction has yet to be identified.…”

Section: How Do Mycobacteria Synthesize Cell Wall Components?mentioning

confidence: 99%

Bacterial Growth and Cell Division: a Mycobacterial Perspective

Hett

Rubín

2008

Microbiol Mol Biol Rev

332

293

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SUMMARY The genus Mycobacterium is best known for its two major pathogenic species, M. tuberculosis and M. leprae, the causative agents of two of the world's oldest diseases, tuberculosis and leprosy, respectively. M. tuberculosis kills approximately two million people each year and is thought to latently infect one-third of the world's population. One of the most remarkable features of the nonsporulating M. tuberculosis is its ability to remain dormant within an individual for decades before reactivating into active tuberculosis. Thus, control of cell division is a critical part of the disease. The mycobacterial cell wall has unique characteristics and is impermeable to a number of compounds, a feature in part responsible for inherent resistance to numerous drugs. The complexity of the cell wall represents a challenge to the organism, requiring specialized mechanisms to allow cell division to occur. Besides these mycobacterial specializations, all bacteria face some common challenges when they divide. First, they must maintain their normal architecture during and after cell division. In the case of mycobacteria, that means synthesizing the many layers of complex cell wall and maintaining their rod shape. Second, they need to coordinate synthesis and breakdown of cell wall components to maintain integrity throughout division. Finally, they need to regulate cell division in response to environmental stimuli. Here we discuss these challenges and the mechanisms that mycobacteria employ to meet them. Because these organisms are difficult to study, in many cases we extrapolate from information known for gram-negative bacteria or more closely related GC-rich gram-positive organisms.

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“…1A). The DD-and LD-transpeptidases use the same amino group in the acyl acceptor for peptide bond formation, corresponding to the ␣-amino group of D-iAsx in E. faecium (15).…”

mentioning

confidence: 99%

“…The LD-transpeptidase from E. faecium, Ldt fm , is the first functionally characterized representative of a conserved family of active site cysteine peptidase (16,17) that include enzymes involved in peptidoglycan cross-linking (15) and in the anchoring of lipoproteins to the peptidoglycan of Escherichia coli (18). Ldt fm exclusively uses donor substrate carrying a tetrapeptide stem (16 (14,16).…”

mentioning

confidence: 99%

Unexpected Inhibition of Peptidoglycan LD-Transpeptidase from Enterococcus faecium by the β-Lactam Imipenem

Mainardi

Hugonnet

Rusconi

et al. 2007

Journal of Biological Chemistry

Self Cite

118

144

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peptide bond in the first step of the DD-transpeptidation reaction, leads to inactivation of the DD-transpeptidases. Because the acylenzymes typically have half-lives in the order of several hours, inactivation of the DD-transpeptidases by ␤-lactams is essentially irreversible in the scale of the generation time of bacteria. The DD-transpeptidases, which are highly redundant enzymes, are collectively the killing target of ␤-lactams, because peptidoglycan cross-linking is essential to the integrity of the cell wall. These enzymes belong to a large family of activesite serine acyl-transferases that bind penicillin covalently and are thus referred to as penicillin-binding proteins (PBPs) (4). The ␤-lactams are one of the oldest and still the most broadly used class of antibiotics for the treatment of severe infections despite the development of several resistance mechanisms, * This work was supported by the Fondation pour la Recherche Mé dicale (Equipe FRM 2006 (Grant DEQ200661107918)) and by NIAID, National Institutes of Health Grant R01 AI45626. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 To whom correspondence should be addressed.

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Specificity of L,D-Transpeptidases from Gram-positive Bacteria Producing Different Peptidoglycan Chemotypes

Cited by 81 publications

References 37 publications

Peptidoglycan Hydrolases of Escherichia coli

Peptidoglycan Hydrolases of Escherichia coli

Bacterial Growth and Cell Division: a Mycobacterial Perspective

Unexpected Inhibition of Peptidoglycan LD-Transpeptidase from Enterococcus faecium by the β-Lactam Imipenem

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