The Enzymatic Synthesis of D-Alanyl-D-alanine. III. On the Inhibition of D-Alanyl-D-alanine Synthetase by the Antibiotic D-Cycloserine<sup>*</sup>

Neuhaus, Francis C.; Lynch, Judy L.

doi:10.1021/bi00892a001

Cited by 186 publications

(167 citation statements)

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“…A noteworthy property of VRSA-9 Ddl was a lag period in the enzymatic assay (Fig. 3A), a phenomenon not seen in VRSA-6 Ddl or in any other D-Ala:D-X ligase (4,23,27). This kinetic behavior is characteristic of hysteretic enzymes which, during catalysis, slowly convert from one kinetic form to another as a a The cytoplasmic peptidoglycan precursors of VRSA-9 grown with or without vancomycin were analyzed as described previously (22 (13,25).…”

Section: Resultsmentioning

confidence: 96%

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Molecular Basis of Vancomycin Dependence in VanA-Type Staphylococcus aureus VRSA-9

Meziane‐Cherif

Saul²,

Moubareck

et al. 2010

J Bacteriol

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The vancomycin-resistant Staphylococcus aureus VRSA-9 clinical isolate was partially dependent on glycopeptide for growth. The responsible vanA operon had the same organization as that of Tn1546 and was located on a plasmid. The chromosomal D-Ala:D-Ala ligase (ddl) gene had two point mutations that led to Q260K and A283E substitutions, resulting in a 200-fold decrease in enzymatic activity compared to that of the wild-type strain VRSA-6. To gain insight into the mechanism of enzyme impairment, we determined the crystal structure of VRSA-9 Ddl and showed that the A283E mutation induces new ion pair/hydrogen bond interactions, leading to an asymmetric rearrangement of side chains in the dimer interface. The Q260K substitution is located in an exposed external loop and did not induce any significant conformational change. The VRSA-9 strain was susceptible to oxacillin due to synthesis of pentadepsipeptide precursors ending in D-alanyl-D-lactate which are not substrates for the ␤-lactam-resistant penicillin binding protein PBP2. Comparison with the partially vancomycin-dependent VRSA-7, whose Ddl is 5-fold less efficient than that of VRSA-9, indicated that the levels of vancomycin dependence and susceptibility to ␤-lactams correlate with the degree of Ddl impairment. Ddl drug targeting could therefore be an effective strategy against vancomycin-resistant S. aureus. Methicillin-resistant

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Section: Resultsmentioning

confidence: 96%

“…The kinetic parameters of the VRSA-9 Ddl reaction were determined using the ADP release spectrophotometric assay previously described (4,23,27). K m for ATP was measured at a fixed 80 mM concentration of D-Ala. VRSA-9 Ddl was used at a concentration of 1.5 M.…”

Section: Methodsmentioning

confidence: 99%

Molecular Basis of Vancomycin Dependence in VanA-Type Staphylococcus aureus VRSA-9

Meziane‐Cherif

Saul²,

Moubareck

et al. 2010

J Bacteriol

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“…Cycloheximide, kanamycin, and streptomycin are also reported to inhibit the protein synthesis, but they do not inhibit the growth of Gram-positive bacteria (Madigan et al, 2000). Cephalexin and cycloserine inhibit the cell wall synthesis, and mitomycin C inhibits DNA synthesis (Iyer and Szybalski, 1964;Morin et al, 1969;Neuhaus and Lynch, 1964). As mentioned above, antibiotics influence biosyntheses, and induced the cystite formation of A. ureafaciens NRIC 0157 T .…”

Section: Discussionmentioning

confidence: 94%

The formation and structures of cystites of Arthrobacter ureafaciens NRIC 0157T induced by antibiotics.

Tanaka

Uchimura

Komagata

2001

J. Gen. Appl. Microbiol.

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The cystite formation of Arthrobacter ureafaciens NRIC 0157 T was induced by some antibiotics, and the addition of tetracycline at a lag phase was effective for cystite formation in YPM liquid medium. Cystites differed from vegetative cells in the cell wall structure, protein content, and water content. Furthermore, the characteristics and structures of cystites induced by tetracycline were similar to those of cystites produced by nutritional imbalance in CT medium. Consequently, various triggers would induce cystite formation. It is interesting that cystite formation was found in part of the Arthrobacter strains and seemed to correlate with the type of peptidoglycan.Key Words--Arthrobacter; Arthrobacter ureafaciens; cell wall; cystites J. Gen. Appl. Microbiol., 47, 85-97 (2001) * Address reprint requests to: Dr. Naoto Tanaka, Laboratory of General and Applied Microbiology, Department of Applied Biology and Chemistry, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan. E-mail: QWP07736@nifty.ne.jp T : Indicates the type strain of a species. Full PaperThis paper deals with the effect of antibiotics on the cystite formation of A. ureafaciens NRIC 0157T and the structures of cell walls and the intracellular structures of cystites and vegetative cells. A correlation between the imbalance growth and the cystite formation of A. ureafaciens NRIC 0157 T is discussed. Materials and MethodsBacterial strains. The following strains were used in this study: (Tanaka et al., 2000), and was composed of 1.0% beef extract (Difco Laboratories), 1.0% peptone (Mikuni Kagaku Sangyo Ltd.), 0.5% NaCl, and 1.5% agar. The pH was adjusted to 7.0 with NaOH.Cultivation. Strains were aerobically precultured in YPM liquid medium with 30 ml L-form test tubes or 500 ml Erlenmeyer flasks at 28 or 37°C. Cells at a late logarithmic phase were collected by centrifugation at 1,600ϫg for 10 min at 20°C and washed twice with saline. The washed cells were suspended in saline, and the suspension was inoculated with 1% (v/v) into fresh YPM liquid medium, CT liquid medium, or other liquid media with a pipette. The liquid media were aerobically incubated at 28 or 37°C for 1 or 2 days up to full growth.Determination of bacterial growth. Bacterial growth in liquid media was determined by absorbance at 660 nm with a single-beam spectrophotometer (NO-VASPEC II, Amersham Pharmacia Biotech, Tokyo, Japan).Investigation of cell shapes. Cell shapes were investigated with a phase-contrast microscope (BX-50, oil immersion lens, Olympus, Tokyo, Japan). The change of cell shapes was monitored at various intervals during the growth.Determination of the Gram reaction by the KOH reaction. An incubated liquid medium was centrifuged at 1,600ϫg for 10 min, and precipitates were used to detect the KOH reaction (Powers, 1995).Cell counts. A total cell number was determined with a Thoma-Zeiss counting chamber, and a viable cell number was determined by the number of colonies appearing on nutrient agar plates...

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“…The acyl carbon atom of the acylphosphate then reacts with the amino group of the second D-Ala to yield a tetrahedral intermediate that dissociates to produce phosphate and D-Ala-D-Ala. Kinetic studies have identified two subsites for D-Ala binding in the active site (11,12). Structural (13)(14)(15)(16)(17)(18) and mutagenesis (19) studies have shown that many of the residues involved in substrate binding and catalysis are conserved in the D-Ala:D-X ligase superfamily.…”

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confidence: 99%

Structural and Functional Characterization of VanG d-Ala:d-Ser Ligase Associated with Vancomycin Resistance in Enterococcus faecalis

Meziane‐Cherif

Saul

Haouz

et al. 2012

Journal of Biological Chemistry

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The Enzymatic Synthesis of D-Alanyl-D-alanine. III. On the Inhibition of D-Alanyl-D-alanine Synthetase by the Antibiotic D-Cycloserine^*

Abstract: Inhibitor studies indicate that both D-alanine (A) binding sites of D-alanyl-D-alanine synthetase are sensitive to D-4-amino-3-isoxazolidone (D-cycloserine [I]). The K for the reaction E

Cited by 186 publications

References 27 publications

Molecular Basis of Vancomycin Dependence in VanA-Type Staphylococcus aureus VRSA-9

Molecular Basis of Vancomycin Dependence in VanA-Type Staphylococcus aureus VRSA-9

The formation and structures of cystites of Arthrobacter ureafaciens NRIC 0157T induced by antibiotics.

Structural and Functional Characterization of VanG d-Ala:d-Ser Ligase Associated with Vancomycin Resistance in Enterococcus faecalis

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The Enzymatic Synthesis of D-Alanyl-D-alanine. III. On the Inhibition of D-Alanyl-D-alanine Synthetase by the Antibiotic D-Cycloserine*

Abstract: Inhibitor studies indicate that both D-alanine (A) binding sites of D-alanyl-D-alanine synthetase are sensitive to D-4-amino-3-isoxazolidone (D-cycloserine [I]). The K for the reaction E

Cited by 186 publications

References 27 publications

Molecular Basis of Vancomycin Dependence in VanA-Type Staphylococcus aureus VRSA-9

Molecular Basis of Vancomycin Dependence in VanA-Type Staphylococcus aureus VRSA-9

The formation and structures of cystites of Arthrobacter ureafaciens NRIC 0157T induced by antibiotics.

Structural and Functional Characterization of VanG d-Ala:d-Ser Ligase Associated with Vancomycin Resistance in Enterococcus faecalis

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The Enzymatic Synthesis of D-Alanyl-D-alanine. III. On the Inhibition of D-Alanyl-D-alanine Synthetase by the Antibiotic D-Cycloserine^*