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VanX, a bacterial D-alanyl-D-alanine dipeptidase: Resistance, immunity, or survival function?
Pages 11028-11032

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From page 11028...
... In the glycopeptide antibiotic producers Streptomyces toyocaensis and Amylocatopsis orientalis, a vanH'4X operon may have convolved with antibiotic biosynthesis genes to provide immunity by reprogramming cell-wall termini to D-Ala-D-lactate as antibiotic biosynthesis is initiated. In the Gram-negative bacterium Escherichia colt, which is never challenged by the glycopeptide antibiotics because they cannot penetrate the outer membrane permeability barrier, the vanX homologue (ddpX, is cotranscribed with a putative dipeptide transport system (ddpABCDF)
From page 11029...
... VanX Homologs in the Bacteria That Produce Vancomycin and Related Glycopeptide Antibiotics. In many instances, bacteria that produce antibiotics have evolved strategies and mechanisms that provide immunity to the action of the antibiotic, and there is a general supposition that immunity mechanisms will have convolved with antibiotic biosynthesis genes to protect the producing organisms (21, 22~.
From page 11030...
... , consistent with a purely degradative function for the DdpX (Table 2~. All of the active site residues and auxiliary residues that maintain the active-site topology in EntVanX are conserved in DdpX, and kinetic analysis also revealed the same substrate specificity and discrimination between peptide bond cleavage (D-Ala-D-Ala)
From page 11031...
... cold chromosome. ddpXABCDF, o4X, hypothetical protein gene product; osmC, gene for osmotically inducible protein; dipeptide permease homolog gene products are indicated.
From page 11032...
... DdpX is a potentially lethal enzyme, because it removes the necessary metabolite D-Ala-D-Ala during peptidoglycan synthesis and is turned on only in the extreme challenge of stationary phase when starvation threatens and the D-Ala-DAla termini of uncrosslinked peptidoglycan strands are retrieved from the periplasm and burned as a metabolic fuel. As additional bacterial genomes are sequenced, more VanX protein homologs are likely to be discovered.


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