Total Synthesis of <i>N</i>-Acetylglucosamine-1,6-anhydro-<i>N</i>-acetylmuramylpentapeptide and Evaluation of Its Turnover by AmpD from Escherichia coli

Hesek, Dušan; Lee, Mijoon; Zhang, Weilie; Noll, Bruce C.; Mobashery, Shahriar

doi:10.1021/ja808498m

Cited by 62 publications

(82 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This high specificity is confirmed by the cleavage of the 1,6-anhydro-MurNAc3L-Ala bond of the 1,6-anhydro-MurNAc-peptide located at the end of isolated PG chains (100). GlcNAc-(134)-1,6-anhydro-MurNActetrapeptide is also recognized as a substrate (97). The accumulation of 1,6-anhydro-MurNAc-tripeptide in an AmpDdeficient mutant suggests that it is the in vivo substrate of AmpD in the PG-recycling process (196).…”

Section: Ampd Anhydro-n-acetylmuramoyl-l-alanine Amidasementioning

confidence: 99%

Peptidoglycan Hydrolases of Escherichia coli

Heijenoort

2011

Microbiol Mol Biol Rev

189

233

View full text Add to dashboard Cite

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.

show abstract

Section: Ampd Anhydro-n-acetylmuramoyl-l-alanine Amidasementioning

confidence: 99%

Peptidoglycan Hydrolases of Escherichia coli

Heijenoort

2011

Microbiol Mol Biol Rev

189

233

View full text Add to dashboard Cite

show abstract

“…The syntheses of 5 and 6 were reported previously by our laboratory. [12, 14] We note that 7 (“tracheal cytotoxin”) is not only the turnover product of 2 , but is also a major turnover product of the sacculus by LTs. Although its synthesis was reported earlier, [15] we now provide its full spectral characterization.…”

mentioning

confidence: 99%

From Genome to Proteome to Elucidation of Reactions for All Eleven Known Lytic Transglycosylases from Pseudomonas aeruginosa

et al. 2017

Self Cite

View full text Add to dashboard Cite

An enzyme superfamily, the lytic transglycosylases (LTs), occupies the space between the two membranes of Gram-negative bacteria. LTs catalyze the non-hydrolytic cleavage of the bacterial peptidoglycan cell-wall polymer. This reaction is central to the growth of the cell wall, for excavating the cell wall for protein insertion, and for monitoring the cell wall so as to initiate resistance responses to cell-wall-acting antibiotics. The nefarious Gram-negative pathogen Pseudomonas aeruginosa encodes eleven LTs. With few exceptions, their substrates and functions are unknown. Each P. aeruginosa LT was expressed as a soluble protein and evaluated with a panel of substrates (both simple and complex mimetics of their natural substrates). Thirty-one distinct products distinguish these LTs with respect to substrate recognition, catalytic activity, and relative exolytic or endolytic ability. These properties are foundational to an understanding of the LTs as catalysts and as antibiotic targets.

show abstract

“…8 Compounds 1c , 2a , and 2c were prepared for this study by known multistep syntheses from our laboratory. 18,19 Compound 4 is commercial.…”

mentioning

confidence: 99%

Muropeptide Binding and the X-ray Structure of the Effector Domain of the Transcriptional Regulator AmpR of Pseudomonas aeruginosa

et al. 2017

Self Cite

View full text Add to dashboard Cite

A complex link between cell-wall recycling/repair and the manifestation of resistance to β-lactam antibiotics in many Enterobacteriaceae and Pseudomonas aeruginosa exists. This process is mediated by specific cell-wall-derived muropeptide products. These muropeptides are internalized into the cytoplasm and bind to the transcriptional regulator AmpR, which controls the cytoplasmic events that lead to expression of β-lactamase, an antibiotic-resistance determinant. The effector-binding domain (EBD) of AmpR was purified to homogeneity. We document that the EBD exists exclusively as a dimer even at a concentration as low as 1 μM. The EBD binds to the suppressor ligand UDP-N-acetyl-β-D-muramyl-L-Ala-γ-D-Glu-meso-DAP-D-Ala-D-Ala (4) and binds to two activator muropeptides, N-acetyl-β-D-glucosamine-(1–4)-1,6-anhydro-N-acetyl-β-D-muramyl-L-Ala-γ-D-Glu-meso-DAP-D-Ala-D-Ala (1c) and 1,6-anhydro-N-acetyl-β-D-muramyl-L-Ala-γ-D-Glu-meso-DAP-D-Ala-D-Ala (2c) as assessed by non-denaturing mass spectrometry. The EBD does not bind to 1,6-anhydro-N-acetyl-β-D-muramyl-L-Ala-γ-D-Glu-meso-DAP (2a). This binding selectivity revises the dogma in the field. The crystal structure of the EBD dimer was solved to 2.2 Å resolution. The EBD crystallizes in a “closed” conformation, in contrast to the “open” structure required to bind the muropeptides. Structural issues of this ligand recognition are addressed by molecular dynamics simulations, which reveal significant differences among the complexes with the effector molecules.

show abstract

Total Synthesis of N-Acetylglucosamine-1,6-anhydro-N-acetylmuramylpentapeptide and Evaluation of Its Turnover by AmpD from Escherichia coli

Cited by 62 publications

References 57 publications

Peptidoglycan Hydrolases of Escherichia coli

Peptidoglycan Hydrolases of Escherichia coli

From Genome to Proteome to Elucidation of Reactions for All Eleven Known Lytic Transglycosylases from Pseudomonas aeruginosa

Muropeptide Binding and the X-ray Structure of the Effector Domain of the Transcriptional Regulator AmpR of Pseudomonas aeruginosa

Contact Info

Product

Resources

About