References of "Frère, Jean-Marie"
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See detailEngineering a Novel Beta-Lactamase by a Single Point Mutation
Jacob, F.; Joris, Bernard ULg; Dideberg, O. et al

in Protein Engineering (1990), 4(1), 79-86

beta-Lactamases are widespread and efficient bacterial enzymes which play a major role in bacterial resistance to penicillins and cephalosporins. In order to elucidate the role of the residues lying in a ... [more ▼]

beta-Lactamases are widespread and efficient bacterial enzymes which play a major role in bacterial resistance to penicillins and cephalosporins. In order to elucidate the role of the residues lying in a conserved loop of the enzymatic cavity of the active-site serine Streptomyces albus G beta-lactamase, modified proteins were produced by oligo-directed mutagenesis. Mutation of Asn116, which lies on one side of the active site cavity pointing to the substrate-binding site, into a serine residue resulted in spectacular modifications of the specificity profile of the enzyme. That replacement yielded an enzyme with a nearly unchanged activity towards good penicillin substrates. In sharp contrast its efficiency in hydrolysing cephalosporins was drastically reduced, the best substrates suffering the largest decrease in the second-order rate constant for serine acylation. In fact that single mutation generated a truly new enzyme behaving exclusively as a penicillinase, a situation which is never encountered to the same degree in any of the numerous naturally occurring variants of class A beta-lactamases. [less ▲]

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See detailThe Diversity of the Catalytic Properties of Class a Beta-Lactamases
Matagne, André ULg; Misselyn-Bauduin, A. M.; Joris, Bernard ULg et al

in Biochemical Journal (1990), 265(1), 131-46

The catalytic properties of four class A beta-lactamases were studied with 24 different substrates. They exhibit a wide range of variation. Similarly, the amino acid sequences are also quite different ... [more ▼]

The catalytic properties of four class A beta-lactamases were studied with 24 different substrates. They exhibit a wide range of variation. Similarly, the amino acid sequences are also quite different. However, no relationships were found between the sequence similarities and the substrate profiles. Lags and bursts were observed with various compounds containing a large sterically hindered side chain. As a group, the enzymes could be distinguished from the class C beta-lactamases on the basis of the kappa cat. values for several substrates, particularly oxacillin, cloxacillin and carbenicillin. Surprisingly, that distinction was impossible with the kappa cat./Km values, which represent the rates of acylation of the active-site serine residue by the beta-lactam. For several cephalosporin substrates (e.g. cefuroxime and cefotaxime) class A enzymes consistently exhibited higher kappa cat. values than class C enzymes, thus belying the usual distinction between 'penicillinases' and 'cephalosporinases'. The problem of the repartition of class A beta-lactamases into sub-classes is discussed. [less ▲]

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See detailBeta-lactamase of Bacillus licheniformis 749/C at 2 A resolution.
Moews, P. C.; Knox, J. R.; Dideberg, O. et al

in Proteins (1990), 7(2), 156-71

Two crystal forms (A and B) of the 29,500 Da Class A beta-lactamase (penicillinase) from Bacillus licheniformis 749/C have been examined crystallographically. The structure of B-form crystals has been ... [more ▼]

Two crystal forms (A and B) of the 29,500 Da Class A beta-lactamase (penicillinase) from Bacillus licheniformis 749/C have been examined crystallographically. The structure of B-form crystals has been solved to 2 A resolution, the starting model for which was a 3.5 A structure obtained from A-form crystals. The beta-lactamase has an alpha + beta structure with 11 helices and 5 beta-strands seen also in a penicillin target DD-peptidase of Streptomyces R61. Atomic parameters of the two molecules in the asymmetric unit were refined by simulated annealing at 2.0 A resolution. The R factor is 0.208 for the 27,330 data greater than 3 sigma (F), with water molecules excluded from the model. The catalytic Ser-70 is at the N-terminus of a helix and is within hydrogen bonding distance of conserved Lys-73. Also interacting with the Lys-73 are Asn-132 and the conserved Glu-166, which is on a potentially flexible helix-containing loop. The structure suggests the binding of beta-lactam substrates is facilitated by interactions with Lys-234, Thr-235, and Ala-237 in a conserved beta-strand peptide, which is antiparallel to the beta-lactam's acylamido linkage; an exposed cavity near Asn-170 exists for acylamido substituents. The reactive double bond of clavulanate-type inhibitors may interact with Arg-244 on the fourth beta-strand. A very similar binding site architecture is seen in the DD-peptidase. [less ▲]

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See detailCHROMOGENIC DEPSIPEPTIDE SUBSTRATES FOR BETA-LACTAMASES AND PENICILLIN-SENSITIVE DD-PEPTIDASES
Adam, M.; Damblon, Christian ULg; PLAITIN, B. et al

in Biochemical Journal (1990), 270(2), 525-529

Various ester and thioester derivatives of hippuric acid have been prepared which were substrates of both beta-lactamases and DD-peptidases. The thioesters were more rapidly hydrolysed by nearly all the ... [more ▼]

Various ester and thioester derivatives of hippuric acid have been prepared which were substrates of both beta-lactamases and DD-peptidases. The thioesters were more rapidly hydrolysed by nearly all the enzymes. Surprisingly, the enzymes acted rather efficiently on substrates which did not contain any chiral centre. [less ▲]

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See detailNucleotide Sequence of the Gene Encoding the Active-Site Serine Beta-Lactamase from Actinomadura R39
Houba, Simone; Willem, Sabine; Duez, Colette ULg et al

in FEMS Microbiology Letters (1989), 65(3), 241-246

The gene encoding the extracellular, active-site serine beta-lactamase of Actinomadura R39, previously cloned into Streptomyces lividans, has the information for the synthesis of a 304 amino acid protein ... [more ▼]

The gene encoding the extracellular, active-site serine beta-lactamase of Actinomadura R39, previously cloned into Streptomyces lividans, has the information for the synthesis of a 304 amino acid protein, the amino terminal region of which has the characteristic features of a signal peptide. The Actinomadura R39 beta-lactamase is another member of the class A beta-lactamases. In particular, it shows high homology with the beta-lactamase of Bacillus licheniformis. [less ▲]

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See detailQuantitative Relationship between Sensitivity to Beta-Lactam Antibiotics and Beta-Lactamase Production in Gram-Negative Bacteria--II. Non-Steady-State Treatment and Progress Curves
Frère, Jean-Marie ULg; Joris, Bernard ULg; Crine, Michel ULg et al

in Biochemical Pharmacology (1989), 38(9), 1427-33

A non-steady-state model is discussed for the study of the interplay between beta-lactamase activity and outer membrane permeability with slowly hydrolysed beta-lactams. The analysis shows: (1) that the ... [more ▼]

A non-steady-state model is discussed for the study of the interplay between beta-lactamase activity and outer membrane permeability with slowly hydrolysed beta-lactams. The analysis shows: (1) that the simple, steady-state model presented in the accompanying paper remains valid as long as kcat (i.e. k3 with chromosome-encoded class C beta-lactamases) is larger than 10(-3)/sec (generation time = 20 min or more); (2) that among the beta-lactam antibiotics studied here, the complete, non-steady-state model needs only be used in the case of aztreonam; (3) that the term "trapping" should be replaced by "formation of a covalent acyl-enzyme" and that such a phenomenon only contributes significantly to the resistance when penetration and hydrolysis are very slow and the periplasmic beta-lactamase concentration is very high. Aztreonam seems to be the only compound which fulfils the first two conditions. [less ▲]

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See detailUnexpected Influence of Ionic Strength on Branched-Pathway Interactions between Beta-Lactamases and Beta-Halogenopenicillanates
De Meester, F.; Matagne, André ULg; Dive, Georges ULg et al

in Biochemical Journal (1989), 257(1), 245-9

Ionic strength strongly influenced the turnover/inactivation ratio in the interaction between beta-halogenopenicillanates and some class A beta-lactamases. This suggested the stabilization of a highly ... [more ▼]

Ionic strength strongly influenced the turnover/inactivation ratio in the interaction between beta-halogenopenicillanates and some class A beta-lactamases. This suggested the stabilization of a highly charged intermediate by solvation. Those data could be interpreted on the basis of a reaction pathway where an episulphonium ion was transiently formed. The various mechanisms proposed for explaining the formation of the dihydrothiazine chromophore are discussed. [less ▲]

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See detailCrystallographic mapping of beta-lactams bound to a d-alanyl-d-alanine peptidase target enzyme
Kelly, Judith A.; Knox, James R.; Zhao, Haiching C. et al

in Journal of Molecular Biology (1989), 209(2), 281-295

X-ray crystallography has been used to examine the binding of three members of the beta-lactam family of antibiotics to the D-alanyl-D-alanine peptidase from Streptomyces R61, a target of penicillins ... [more ▼]

X-ray crystallography has been used to examine the binding of three members of the beta-lactam family of antibiotics to the D-alanyl-D-alanine peptidase from Streptomyces R61, a target of penicillins. Cephalosporin C, the monobactam analog of penicillin G and (2,3)-alpha-methylene benzylpenicillin have been mapped at 2.3 A resolution in the form of acyl-enzyme complexes bound to serine 62. On the basis of the positions of these inhibitors, the binding of a tripeptide substrate for the enzyme, L-lysyl-D-alanyl-D-alanine, has been modeled in the active site. The binding of both inhibitors and substrate is facilitated by hydrogen-bonding interactions with a conserved beta-strand (297-303), which is antiparallel to the beta-lactam's acylamide linkage or the substrate's peptide bond. The active site is similar to that in beta-lactamases. [less ▲]

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See detailCloning and amplified expression in Streptomyces lividans of the gene encoding the extracellular beta-lactamase of Actinomadura R39
Fraipont, Claudine ULg; Duez, Colette ULg; Matagne, André ULg et al

in Biochemical Journal (1989), 262(3), 849-854

By using the promoter-probe plasmid pIJ424, genomic DNA fragments of Actinomadura R39 were shown to have promoter activity in Streptomyces lividans. The same 100-200-copy-number plasmid was used to clone ... [more ▼]

By using the promoter-probe plasmid pIJ424, genomic DNA fragments of Actinomadura R39 were shown to have promoter activity in Streptomyces lividans. The same 100-200-copy-number plasmid was used to clone in S. lividans TK24, the gene that encodes the Actinomadura R39, β-lactamase. Gene cloning resulted in an amplified expression of the , β lactamase when compared with the amounts of enzyme produced by the original strain (1 mg versus 0.008 mg . litre of culture-1). [less ▲]

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See detailSequence and Comparative Analysis of Three Enterobacter Cloacae Ampc Beta-Lactamase Genes and Their Products
Galleni, Moreno ULg; Lindberg, F.; Normark, S. et al

in Biochemical Journal (1988), 250(3), 753-60

The sequences of three Enterobacter cloacae ampC beta-lactamase genes have been determined. The deduced amino acid sequences are very similar: out of a total of 361 residues, only eight positions were ... [more ▼]

The sequences of three Enterobacter cloacae ampC beta-lactamase genes have been determined. The deduced amino acid sequences are very similar: out of a total of 361 residues, only eight positions were found to be variable, and several mutations yielded residues with very similar properties. The kinetic properties of two of the enzymes were not significantly different. The three enzymes also exhibited a high degree of homology (greater than 70%) with the ampC beta-lactamases of Escherichia coli K12 and Citrobacter freundii, confirming the homogeneity of class-C beta-lactamases. [less ▲]

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See detailUsing X-ray diffraction results and computer graphics to design beta-lactams
Kelly, Judith A.; Knox, J. R.; Moews, P. C. et al

in Kansenshogaku Zasshi = Journal of the Japanese Association for Infectious Diseases (1988), 62 Suppl

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See detailThe Active-Site-Serine Penicillin-Recognizing Enzymes as Members of the Streptomyces R61 Dd-Peptidase Family
Joris, Bernard ULg; Ghuysen, Jean-Marie ULg; Dive, Georges ULg et al

in Biochemical Journal (1988), 250(2), 313-324

Homology searches and amino acid alignments, using the Streptomyces R61 DD-peptidase/penicillin-binding protein as reference, have been applied to the beta-lactamases of classes A and C, the Oxa-2 beta ... [more ▼]

Homology searches and amino acid alignments, using the Streptomyces R61 DD-peptidase/penicillin-binding protein as reference, have been applied to the beta-lactamases of classes A and C, the Oxa-2 beta-lactamase (considered as the first known member of an additional class D), the low-Mr DD-peptidases/penicillin-binding proteins (protein no. 5 of Escherichia coli and Bacillus subtilis) and penicillin-binding domains of the high-Mr penicillin-binding proteins (PBP1A, PBP1B, PBP2 and PBP3 of E. coli). Though the evolutionary distance may vary considerably, all these penicillin-interactive proteins and domains appear to be members of a single superfamily of active-site-serine enzymes distinct from the classical trypsin or subtilisin families. The amino acid alignments reveal several conserved boxes that consist of strict identities or homologous amino acids. The significance of these boxes is highlighted by the known results of X-ray crystallography, chemical derivatization and site-directed-mutagenesis experiments. [less ▲]

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See detailStructure-Activity Relationships in the Beta-Lactam Family: An Impossible Dream
Frère, Jean-Marie ULg; Joris, Bernard ULg; Varetto, Louis ULg et al

in Biochemical Pharmacology (1988), 37(1), 125-32

The difficulty of establishing structure-activity relationships in the beta-lactam family of antibiotics stems from the fact that: (1) The targets in various bacteria exhibit widely different ... [more ▼]

The difficulty of establishing structure-activity relationships in the beta-lactam family of antibiotics stems from the fact that: (1) The targets in various bacteria exhibit widely different sensitivities. (2) Some bacteria produce beta-lactamases, enzymes capable of destroying the antibiotics. The rates of the reactions with the beta-lactamases and the target enzymes are not necessarily related. (3) In Gram-negative bacteria, the diffusion rate through the outer membrane varies independently from the two other factors. [less ▲]

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See detailPenicillin-recognizing enzymes
Frère, Jean-Marie ULg; Joris, Bernard ULg; Dideberg, Otto et al

in Biochemical Society Transactions (1988), 16(6), 934-938

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See detailChromosome-encoded beta-lactamases of Citrobacter diversus. Interaction with beta-iodopenicillanate and labelling of the active site.
Amicosante, G; Oratore, A; Joris, Bernard ULg et al

in Biochemical Journal (1988), 254(3), 891-3

Both forms of the chromosome-encoded beta-lactamase of Citrobacter diversus react with beta-iodopenicillanate at a rate characteristic of class A beta-lactamases. The active site of form I was labelled ... [more ▼]

Both forms of the chromosome-encoded beta-lactamase of Citrobacter diversus react with beta-iodopenicillanate at a rate characteristic of class A beta-lactamases. The active site of form I was labelled with the same reagent. The sequence of the peptide obtained after trypsin hydrolysis is identical with that of a peptide obtained in a similar manner from the chromosome-encoded beta-lactamase of Klebsiella pneumoniae. [less ▲]

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See detailBeta-Lactamases as the Main Resistance Factor to Penicillin-Related Antibiotics
Frère, Jean-Marie ULg; Joris, Bernard ULg

in Annales de Biologie Clinique (1988), 46(2), 151-6

The interplay between the three factors involved in the resistance of bacteria to beta-lactam antibiotics (sensitivity of target, synthesis of beta-lactamase, permeability barrier) is analysed and ... [more ▼]

The interplay between the three factors involved in the resistance of bacteria to beta-lactam antibiotics (sensitivity of target, synthesis of beta-lactamase, permeability barrier) is analysed and discussed on the basis of a simple kinetic model. The three factors do not act independently. In Gram-negative bacteria, the permeability barrier is only significant when the bacterial cell also produces a beta-lactamase. Special attention is devoted to cases where large periplasmic beta-lactamase concentrations prevail, a situation which has been observed in some clinical isolates. [less ▲]

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See detailBeta-Lactamase-induced resistance
Frère, Jean-Marie ULg; Joris, Bernard ULg

in Actor, Paul; Daneo-Moore, Lolita; Higgins, Michael, L. (Eds.) et al Antibiotic Inhibition of Bacterial Cell Surface Assembly and Function (1988)

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See detailThe Importance of the Negative Charge of Beta-Lactam Compounds for the Inactivation of the Active-Site Serine Dd-Peptidase of Streptomyces R61
Varetto, Louis ULg; Frère, Jean-Marie ULg; Ghuysen, Jean-Marie ULg

in FEBS Letters (1987), 225(1-2), 218-222

The interaction between the Streptomyces R61 penicillin-sensitive DD-peptidase and deacetyl-cephalosporin C or its lactone derivative has been studied at different pH values. The results show the ... [more ▼]

The interaction between the Streptomyces R61 penicillin-sensitive DD-peptidase and deacetyl-cephalosporin C or its lactone derivative has been studied at different pH values. The results show the importance of an enzyme group of pK approximately equal to 9 which might form an ion pair with the free carboxylate of the former compound. This electrostatic interaction is shown to contribute to the formation of the first, non-covalent enzyme-inactivator complex by a factor of at least 50. [less ▲]

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See detailCloning and amplified expression in streptomyces-lividans of the gene encoding the extracellular beta-lactamase from streptomyces-cacaoi
Lenzini, Mauro V; Nojima, Shiego; Dusart, Jean et al

in Journal of General Microbiology (1987), 133(10), 2915-2920

A 19 kb SphI DNA fragment containing the gene for the extracellular active-site serine beta-lactamase of Streptomyces cacaoi KCC-SO352 was cloned in Streptomyces lividans TK24 using the high-copy-number ... [more ▼]

A 19 kb SphI DNA fragment containing the gene for the extracellular active-site serine beta-lactamase of Streptomyces cacaoi KCC-SO352 was cloned in Streptomyces lividans TK24 using the high-copy-number plasmid pIJ702 as vector. A 30-fold higher yield of beta-lactamase was obtained from S. lividans strain ML1, carrying the recombinant plasmid pDML51, than from S. cacaoi grown under optimal production conditions. In all respects (molecular mass, isoelectric point, kinetics of inhibition by beta-iodopenicillanate) the overproduced S. lividans ML1 beta-lactamase was identical to the original S. cacaoi enzyme. A considerable reduction of beta-lactamase production was caused by elimination of a 12.8 kb portion of the 19 kb DNA fragment by cleavage at an internal SphI site located more than 3 kb upstream of the beta-lactamase structural gene. The beta-lactamase gene was located within a 1.8 NcoI-BclI fragment but when this fragment was cloned in S. lividans pIJ702, the resulting strain produced hardly any more beta-lactamase than the original S. cacaoi. [less ▲]

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See detailNucleotide sequence of the gene encoding the Streptomyces albus G beta-lactamase precursor
Dehottay, Philippe; Dusart, Jean; De Meester, Fabien et al

in European Journal of Biochemistry (1987), 166(2), 345-350

A 1400-base DNA fragment, which contains the gene encoding the extracellular active-site serine beta-lactamase of Streptomyces albus G previously cloned into Streptomyces lividans [Dehottay et al. (1986 ... [more ▼]

A 1400-base DNA fragment, which contains the gene encoding the extracellular active-site serine beta-lactamase of Streptomyces albus G previously cloned into Streptomyces lividans [Dehottay et al. (1986) Gene 42, 31-36], was sequenced. The gene codes for a 314-amino-acid precursor, the N-terminal region of which has the characteristics of a signal peptide. The beta-lactamase as excreted by the host strain S. lividans PD6 has a ragged N-terminus, indicating either the presence of a leader peptidase of poor specificity or the action of an aminopeptidase. The primary structure (as deduced from the nucleotide sequence) was confirmed by amino acid sequencing of a 16-residue stretch at the amino terminus of the protein, a 12-residue stretch containing the active-site serine [De Meester et al. (1987) Biochem. J. 244, 427-432] and a 23-residue stretch obtained by trypsin digestion of the protein. The beta-lactamase belongs to class A, has three half-cystine residues (one of which occurs on the amino side of the active-site serine) and is inactivated by thiol reagents. Putative ribosome binding site and terminator region were identified. [less ▲]

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