References of "Frère, Jean-Marie"
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See detailStability of D-5,5-dimethyl-delta2-thiazoline-4-carboxylic acid in relation to its possible occurrence as a degradation product of penicillin by the exocellular DD-carboxypeptidase-transpeptidase from Streptomyces R61 and the membrane-bound dd-carboxypeptidase from Bacillus stearothermophilus
Adriaens, Paul; Meesschaert, Boudewijn; Frère, Jean-Marie ULg et al

in Journal of Biological Chemistry (1978), 253(10), 3660-3665

The stability of D-5,5-dimethyl-delta2-thiazoline-4-carboxylic acid has been studied under various conditions. In 10 mM cacodylate, pH 6.5, and at 55 degrees C, D-5,5-dimethyl-delta2-thiazoline-4 ... [more ▼]

The stability of D-5,5-dimethyl-delta2-thiazoline-4-carboxylic acid has been studied under various conditions. In 10 mM cacodylate, pH 6.5, and at 55 degrees C, D-5,5-dimethyl-delta2-thiazoline-4-carboxylic acid (at concentrations lower than 1 mM) is hydrolyzed into N-formyl-D-penicillamine with a half-life of 3 to 4 min. On this basis, it is very unlikely that D-5,5-dimethyl-delta2-thiazoline-4-carboxylic acid could be one of the end products resulting from the cleavage of benzylpenicillin by the DD-carboxypeptidase of Bacillus stearothermophilus (as reported by Hammarstrom and Strominger (1976) J. Biol. Chem. 251, 7947--7949). In 3 mM phosphate, pH 7.5, and at 37 degrees C, D-5,5-dimethyl-delta2-thiazoline-4-carboxylic acid (at concentrations lower than 1 mM) has a half-life of 45 min. On the basis of kinetic experiments carried out under these conditions with phenoxymethylpenicillin and the DD-carboxypeptidase-transpeptidase of Streptomyces R61, it is concluded that the primary product which arises from the thiazolidine moiety of the antibiotic molecule and gives rise to N-formyl-D-penicillamine, has a half-life of 10 min, a value which is not compatible with the hypothesis that D-5,5-dimethyl-delta2-thiazoline-4-carboxylic acid would be an intermediate involved in the fragmentation pathway. [less ▲]

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See detailInteraction between penicillin and the DD-carboxypeptidase of the unstable L-form of Proteus mirabilis strain 19
Schilf, Wolfgang; Frere, Philippe; Frère, Jean-Marie ULg et al

in European Journal of Biochemistry (1978), 85(2), 325-330

Binding of penicillin to the DD-carboxypeptidase of the unstable spheroplast L-form of Proteus mirabilis results in the rapid formation of a modified enzyme-inhibitor complex which in turn undergoes rapid ... [more ▼]

Binding of penicillin to the DD-carboxypeptidase of the unstable spheroplast L-form of Proteus mirabilis results in the rapid formation of a modified enzyme-inhibitor complex which in turn undergoes rapid decay into reactivated enzyme and an antibiotically inactive penicillin degradation product. Major antibiotic metabolites recovered from such interactions were benzylpenicilloic acid and phenoxymethylpenicilloic acid from benzylpenicillin and phenoxymethylpenicillin, respectively, suggesting a second enzymic function of the DD-carboxypeptidase as a penicillinase of low efficiency. Statistical analyses made with the help of a linear regression program show that the enzyme interacts with the substrate UDP-N-acetylmuramoyl-L-alanyl-D-gamma-glutamyl-(L)-meso-2,6-diaminopimelyl -(L)-D-alanyl-D-alanine and either benzympenicillin or carbenicillin in a non-competitive manner. [less ▲]

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See detailLarge Scale Preparation of Purified Exocellular DD-carboxypeptidase-Transpeptidase of Streptomyces Strain R61
Fossati, P.; Saint-Ghislain, M.; Sicard, P. J. et al

in Biotechnology and Bioengineering (1978), 20

The exocellular DD-carboxypeptidase–transpeptidase that Streptomyces R61 excretes during growth has been produced in large fermentation units of 15 m3 total capacity. The yield from 15,000 liter culture ... [more ▼]

The exocellular DD-carboxypeptidase–transpeptidase that Streptomyces R61 excretes during growth has been produced in large fermentation units of 15 m3 total capacity. The yield from 15,000 liter culture filtrate was 1.080 g purified enzyme (92% purity) with a total recovery of 29% and at least a 2000-fold increased specific activity. [less ▲]

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See detailThe exocellular DD-carboxypeptidase-endopeptidase of Streptomyces albus G. Interaction with beta-lactam antibiotics.
Frère, Jean-Marie ULg; Geurts, Francine; Ghuysen, Jean-Marie ULg

in Biochemical Journal (1978), 175(3), 801-805

Kinetically, the three-step model proposed for the interaction between beta-lactam antibiotics and the exocellular DD-carboxypeptidases-transpeptidases of Streptomyces R61 and Actinomadura R39 [Frère ... [more ▼]

Kinetically, the three-step model proposed for the interaction between beta-lactam antibiotics and the exocellular DD-carboxypeptidases-transpeptidases of Streptomyces R61 and Actinomadura R39 [Frère, Ghuysen & Iwatsubo (1975) Eur. J. Biochem. 57, 343--357; Fuad, Frère, Ghuysen, Duez & Iwatsubo (1976) Biochem. J. 155, 623--629] applies to the interaction between the much less penicillin-sensitive exocellular DD-carboxypeptidase-endopeptidase of Streptomyces albus G and at least phenoxymethylpenicillin, cephalothin and cephalosporin C. The penicillin resistance of the albus G enzyme is mainly due to the low efficiency with which the first reversible complex formed with the antibiotic (complex EI) undergoes transformation into a second more stable complex EI*. Analysis of the ternary interaction between enzyme, NalphaNepsilon-diacetyl-L-lysyl-D-alanyl-D-alanine (Ac2-L-Lys-D-Ala-D-Ala) and cephalosporin C indicates a non-competitive mechanism. [less ▲]

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See detailThe exocellular DD-carboxypeptidase-endopeptidase from Streptomyces albus Gl. Purification and chemical properties
Duez, Colette ULg; Frère, Jean-Marie ULg; Geurts, Francine et al

in Biochemical Journal (1978), 175(3), 793-800

The exocellular DD-carboxypeptidase-endopeptidase of Streptomyces albus G was purified to protein homogeneity and compared with the exocellular DD-carboxypeptidases-transpeptidases of Streptomyces R61 and ... [more ▼]

The exocellular DD-carboxypeptidase-endopeptidase of Streptomyces albus G was purified to protein homogeneity and compared with the exocellular DD-carboxypeptidases-transpeptidases of Streptomyces R61 and Actinomadura R39. The S. albus G enzyme, as it is isolated, occurs in two forms. Enzyme I (30% of the total amount) and enzyme II (70% of the total amount) are identical in all respects, except that, by polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate, enzyme I has an apparent mol. wt. (9000) that is half of that found by molecular-sieve filtration under non-denaturing conditions. Irrespective of the technique used, enzyme II has an apparent mol. wt. of about 18500. [less ▲]

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See detailThe peptidoglycan crosslinking enzyme system in Streptomyces R61, K15 and rimosus. Immunological studies
Nguyen-Distèche, Martine ULg; Frère, Jean-Marie ULg; Dusart, Jean et al

in European Journal of Biochemistry (1977), 81(1), 29-32

The exocellular DD-carboxypeptidases from Streptomyces R61, K 15, the lysozyme-releasable DD-carboxypeptidases from Streptomyces R61, K15 and rimosus, and the membrane-bound DD-carboxypeptidase of ... [more ▼]

The exocellular DD-carboxypeptidases from Streptomyces R61, K 15, the lysozyme-releasable DD-carboxypeptidases from Streptomyces R61, K15 and rimosus, and the membrane-bound DD-carboxypeptidase of Streptomyces K15 are immunologically related to each other. [less ▲]

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See detailFate of thiazolidine ring during fragmentation of penicillin by exocellular DD-carboxypeptidase-transpeptidase of Streptomyces R61
Frère, Jean-Marie ULg; Ghuysen, Jean-Marie ULg; Vanderhaeghe, Hubert et al

in Nature (1976), 260(5550), 451-454

LIKE various beta-lactamases, acylases and esterases1, the exocellular DD-carboxypeptidase-transpeptidase of Streptomyces R61 degrades benzylpenicillin and other beta-lactam antibiotics2-4. The R61 enzyme ... [more ▼]

LIKE various beta-lactamases, acylases and esterases1, the exocellular DD-carboxypeptidase-transpeptidase of Streptomyces R61 degrades benzylpenicillin and other beta-lactam antibiotics2-4. The R61 enzyme, however, markedly differs from the other penicillin-degrading enzymes in causing fragmentation of the penicillin nucleus. By using 8-14C-benzylpenicillin (benzyl labelled) as substrate, one of the fragments produced was shown to be 14C-phenylacetylglycine5. The reaction with the R61 enzyme is also peculiar in that it is a slow process. This is because of the long half life of the stoichiometnc complex transitorily formed between the antibiotic and the enzyme. Thus, for example, the value of the half life for the complex formed with benzylpenicillin is 80 min in 10 mM phosphate buffer (pH 7.0) and at 37 °C. As breakdown of the complex proceeds, however, phenylacetylglycine (when benzylpenicillin is used as substrate) is released and the enzyme concomitantly recovers its ability to bind penicillin. We have now characterised the fragment (hereby designated as the Y product) arising from the thiazolidine ring of penicillin as a result of the fragmentation of the antibiotic molecule by the R61 enzyme. [less ▲]

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See detail[51] Exocellular dd-carboxypeptidases-transpeptidases from Streptomyces
Frère, Jean-Marie ULg; Leyh-Bouille, Mélina; Ghuysen, Jean-Marie ULg et al

in Lorand, Laszlo (Ed.) Part B: Proteolytic Enzymes (1976)

Strains R39 and R61 are soil isolates. Their designations are arbitrary. In strain R39, the cross-link between the peptide units of the wall peptidoglycan extends from the C-terminal D-alanine of one unit ... [more ▼]

Strains R39 and R61 are soil isolates. Their designations are arbitrary. In strain R39, the cross-link between the peptide units of the wall peptidoglycan extends from the C-terminal D-alanine of one unit to the amino group at the D-center of meso-diaminopimelic acid of another unit (peptidoglycan of chemotype I). The interpeptide bond is in position to a free carboxyl group. In strain R61, the cross-link extends from a C-terminal D-alanine of a peptide unit to a glycine residue attached to the amino group of LL-diaminopimelic acid of another peptide unit (peptidoglycan of chemotype II). The exocellular DD carboxypeptidases-transpeptidases produced by both strains catalyze hydrolysis, react with β-lactam antibiotics. This chapter explains the assay methods for DD-Carboxypeptidase activity like the standard reaction, chemical estimation of free Alanine, as well as, assay method for β-Lactamase. It also discusses the Excretion of DD-Carboxypeptidase-Transpeptidase and β -Lactamase by Streptomyces R39, Excretion of DD-Carboxypeptidase-Transpeptidase and β-Lactamase by Streptomyces R61, purification of the DD-Carboxypeptidase-Transpeptidase from Streptomyces R39 (for 500 Liters of Culture Fluid), Purification of the DD-Carboxypeptidase-Transpeptidase from Streptomyces R61 (for 400 Liters of Culture Fluid), Physicochemical Properties of DD-Carboxypeptidases-Transpeptidases from Streptomyces R39 and R61, Interaction between DD-Carboxypeptidases-Transpeptidases from Streptomyces R39 and R61 and β-Lactam Antibiotics , Titration of DD-Carboxypeptidases-Transpeptidases from Streptornyces R39 and R61 by β-Lactam Antibiotics, Hydrolysis Reactions Catalyzed by the DD-Carboxypeptidases-Transpeptidases from Streptomyces R39 and R61, Concomitant Hydrolysis and Transfer Reactions Involving Distinct Donor and Acceptor Peptides, Catalyzed by the DD-Carboxypeptidases-Transpeptidases from Streptonayces R39 and R61, Concomitant Hydrolysis and Transfer Reactions Catalyzed by the DD-Carboxypeptidases-Transpeptidases from Streptomyces R39 and R61 and in Which the Same Peptide Acts as Donor and Acceptor and Inhibition of DD-Carboxypeptidases-Transpeptidases from Streptomyces R39 and R61 by β-Lactam Antibiotics in the Presence of Substrates. Copyright © 1976 Published by Elsevier Inc. [less ▲]

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See detailMode of interaction between β-lactam antibiotics and the exocellular DD-carboxypeptidase--transpeptidase from Streptomyces R39
Fuad, Noha; Frère, Jean-Marie ULg; Ghuysen, Jean-Marie ULg et al

in Biochemical Journal (1976), 155(3), 623-629

The exocellular DD-carboxypeptidase-transpeptidase of Streptomyces R39 is inhibited by beta-lactam antibiotics according to the same general scheme of reaction as the exocellular DD-carboxypeptidase ... [more ▼]

The exocellular DD-carboxypeptidase-transpeptidase of Streptomyces R39 is inhibited by beta-lactam antibiotics according to the same general scheme of reaction as the exocellular DD-carboxypeptidase-transpeptidase of Streptomyces R61. However, the values for the kinetic constants involved in the reaction are very different for the two enzymes and provide an explanation for the observation that the R39 enzyme is more sensitive to beta-lactam antibiotics than the R61 enzyme. Further, particular beta-lactams influence the kinetic constants to different extents depending on the source of the enzyme, so that a physical basis for the spectrum of antibiotic activity against particular enzyme systems is provided. [less ▲]

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See detailDegradation of benzylpenicillin by the exocellular DD-carboxypeptidase-transpeptidase from Streptomyces R 61
Frère, Jean-Marie ULg; Adriaens, P.; Degelaen, J. et al

in Archives Internationales de Physiologie et de Biochimie (1975), 83(5), 905-907

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See detailKinetics of interaction between the exocellular DD-carboxypeptidase-transpeptidase from Streptomyces R61 and beta-lactam antibiotics. A choice of models
Frère, Jean-Marie ULg; Ghuysen, Jean-Marie ULg; Iwatsubo, Motohiro

in European Journal of Biochemistry (1975), 57(2), 343-351

The simplest model for the interaction between the exocellular DD-carboxypeptidase-transpeptidase from Streptomyces R61 and beta-lactam antibiotics involves the three following steps: (a) the formation of ... [more ▼]

The simplest model for the interaction between the exocellular DD-carboxypeptidase-transpeptidase from Streptomyces R61 and beta-lactam antibiotics involves the three following steps: (a) the formation of a reversible equimolar enzyme - antibiotic complex; (b) the irreversible transformation of this complex into a modified enzyme - antibiotic complex; and (c) the breakdown of this latter complex and the concomitant release of a regenerated enzyme and a modified antibiotic molecule. The dissociation constant for step 1 and the rate constants for steps 2 and 3 were measured with various beta-lactam antibiotics. With antibiotic such as benzylpenicillin, which behaves as a good 'substrate', steps 1 and 2 occur at enzymic velocities, whereas step 3 occurs at a very low velocity and hence is responsible for the low efficiency of the overall process. [less ▲]

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See detailInteraction between the exocellular DD-carboxypeptidase-transpeptidase from Streptomyces R61, substrate and beta-lactam antibiotics. A choice of models
Frère, Jean-Marie ULg; Ghuysen, Jean-Marie ULg; Perkins, Harold R

in European Journal of Biochemistry (1975), 57(2), 353-359

The interaction between the exocellular DD-carboxypeptidase-transpeptidase of Streptomyces R61 and beta-lactam antibiotics is a multistep process during which a rather stable enzyme - antibiotic complex ... [more ▼]

The interaction between the exocellular DD-carboxypeptidase-transpeptidase of Streptomyces R61 and beta-lactam antibiotics is a multistep process during which a rather stable enzyme - antibiotic complex is formed. This mechanism of interaction is compatible with Lineweaver-Burk plots that are typical of a competitive inhibition of the hydrolysis of the peptide donor by the antibiotic. In fact, however, the same Lineweaver-Burk plots can be obtained on the basis of a non-competitive type of inhibition. At present, a choice between the two models cannot be made. [less ▲]

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See detailA donor-acceptor substrate of the exocellular DD-carboxypeptidase-transpeptidase from Streptomyces R61
Zeiger, Allen R; Frère, Jean-Marie ULg; Ghuysen, Jean-Marie ULg et al

in FEBS Letters (1975), 52(2), 221-225

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See detailBeta-lactamases (Actinomycetes species)
Johnson, Kenneth; Duez, Colette ULg; Frère, Jean-Marie ULg et al

in Methods in Enzymology (1975), XLIII

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See detailInteraction between beta-lactam antibiotics and exocellular DD-carboxypeptidase-transpeptidase of Streptomyces R61
Frère, Jean-Marie ULg; Leyh-Bouille, Mélina; Ghuysen, Jean-Marie ULg et al

in European Journal of Biochemistry (1974), 50(1), 203-214

On the basis of steady-state kinetics, inhibition of the exocellular dd-carboxypeptidase-trans-peptidase of Streptomyces R61 by β-lactam antibiotics was competitive with regard to the donor substrate ... [more ▼]

On the basis of steady-state kinetics, inhibition of the exocellular dd-carboxypeptidase-trans-peptidase of Streptomyces R61 by β-lactam antibiotics was competitive with regard to the donor substrate. However, the complexes formed between the Streptomyces R61 enzyme and various β-lactam antibiotics were relatively stable, exhibiting half-lives of 40 to 80 min at 37°C and neutral pH. During breakdown of the complexes the protein underwent reactivation, whereas the released antibiotic molecule was chemically altered. With [14C]benzylpenicillin, the released compound was neither benzylpenicillin nor benzylpenicilloic acid. The properties of the Streptomyces R61 enzyme β-lactam antibiotic complexes were compared with those of the complexes formed between the same antibiotics and either the membrane-bound transpeptidase from Streptomyces R61 or the exocellular dd-carboxypeptidase-transpeptidase of Streptomyces R39. [less ▲]

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See detailMolecular weight, amino acid composition and physicochemical properties of the exocellular DD-carboxypeptidase-transpeptidase of Streptomyces R39
Frère, Jean-Marie ULg; Moreno, Ramon; Ghuysen, Jean-Marie ULg

in Biochemical Journal (1974), 143(1), 233-240

The exocellular dd-carboxypeptidase-transpeptidase from Streptomyces R39 was purified to protein homogeneity and in milligram amounts. The isolated enzyme consisted of one polypeptide chain of molecular ... [more ▼]

The exocellular dd-carboxypeptidase-transpeptidase from Streptomyces R39 was purified to protein homogeneity and in milligram amounts. The isolated enzyme consisted of one polypeptide chain of molecular weight about 53300. Its amino acid composition and several physicochemical properties were determined and compared with those of the exo-cellular dd-carboxypeptidase-transpeptidase from Streptomyces R61. [less ▲]

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