Alanine racemase and

D-alanine production by alanine racemase, and then preferential excretion of the D-alanine across the cell membrane into the medium. 

Inhibits the enzymes alanine racemase and D-alanyl-D-alanyl synthetase that are responsible for producing the dipeptide D-alanyl-D-alanine, a precursor of the pentapeptide chain in cell wall formation. It is believed that the rigid structure of the isoxazole ring gives the drug a better chance of binding to the enzyme than the more flexible structure of D-alanine. 

Inhibition of cell wall peptidoglycan synthesis D-cycIoserine Early biosynthetic stage competitive inhibition of (i) alanine racemase and (ii) D-alanine synthetase (ligase)... 

Scheme 13.22 Amino acid racemization by (a) PLP-dependent alanine racemase and (b) PLP-independent a-amino acid racemase.

This asymmetry with respect to the catalytic bases in mandelate racemase is formally analogous to alanine racemase, and indeed the overshoots with mandelate racemase are highly asymmetric as with alanine racemase (Table 7.2) [10]. The... 

Figure 17-3. A, Preparation of [4S-2H]-NADH by coupling of alanine racemase and L-alanine dehydrogenase. B, In situ determination of stereospecificity of H-transfer by H-NMR. AlaR, AlaDH, and DH represent alanine racemase, L-alanine dehydrogenase, and dehydrogenase, respectively.

It will be recalled that some of these UDP-N-acetylmuramyl compounds were isolated by Park and Johnson, from penicillin-inhibited cells of Staphylococcus aureus, at about the same time that Leloir s group isolated the first sugar nucleotide, UDP-D-glucose, from yeast. Other conditions also produce accumulation of some of these compounds. Thus, D-cycloserine is known to induce an accumulation of UDP-iV-acetylmuramy-tripeptide in S. aureus this is easily explained by the observation that D-cycloserine is a powerful, competitive inhibitor both of alanine racemase and D-alanyl-D-alanine synthetase. ... 

Mustata, G. and Briggs, J.M. (2004) Cluster analysis of water molecules in alanine racemase and their putative structural role. Protein Engineering, Design and Selection, 17, 223—234. 

D-Cycloserine 239 is a well-known antibiotic which inhibits alanine racemase and D-alanyl-D-alanine ligase [117]. The reactivity of the y-lactam carbonyl towards nucleophilic reagents is enhanced by the electronegative oxygen substituent. 

Over the last fifteen years, a large number of terminal phosphonopeptides [162-165] have been synthesised and tested as potential inhibitors of the early stages in peptidoglycan biosynthesis. For instance, alophosphin (313) inhibits alanine racemase, and has emerged as an excellent antibacterial agent [163]. 

The bacterial cell wall is the first line of defense against environmental stress in gram-positive bacteria. Thus, selection schemes that change the cell wall structure can potentially make cells more resistant to environmental stress. D-cycloserine is an antibiotic that inhibits alanine racemase and D-alanine D-alanine ligase, both involved in cell wall biosynthesis. Mutants resistant to this antibiotic have been isolated in a number of gram-positive species and shown to have differences in surface properties (Clark Young, 1977 Reitz, Slade, Neuhaus, 1967). We have used D-cycloserine as a selective agent to directly select mutants in a variety of strains and found that the mutants obtained have properties useful in industrial fermentation processes. 

The mechanism of cyclosporin biosynthesis is now widely understood, as key enzymes Bmt synthase, alanine racemase. and cyclosporin synthetase are necessary to build up the cyclic undecapeptide. Still more experimental work has to be performed on the biosynthesis of the peptolide SDZ 214 103 to fiilly characterize the enzymes and the pathways involved. 

The free amino boronic acid CH3CH(NH2)B(OH)2, an alanine analog, survives for a few hours after its N-silylated-O-isopropyl protected form contacts water. It is an inhibitor of Bacillus stearothermophilus alanine racemase and Salmonella typhimurium D-alanine D-alanine ligase [66]. 

D-cycloserine inhibits conversion of L-alanine into D-alanine by alanine racemase and coupling of two D-alanines by D-alanine D-alanine ligase... 

The Cofactor Pyridoxal 5 -phosphate from Organic Models to Alanine Racemase and Aspartate Aminotransferase... 

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