References of "Dideberg, O"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailCompetitive inhibitors of the CphA metallo-beta-lactamase from Aeromonas hydrophila
Horsfall, L. E.; Garau, G.; Lienard, B. M. et al

in Antimicrobial Agents and Chemotherapy (2007), 51(6), 2136-2142

Various inhibitors of metallo-beta-lactamases have been reported; however, none are effective for all subgroups. Those that have been found to inhibit the enzymes of subclass B2 (catalytically active with ... [more ▼]

Various inhibitors of metallo-beta-lactamases have been reported; however, none are effective for all subgroups. Those that have been found to inhibit the enzymes of subclass B2 (catalytically active with one zinc) either contain a thiol (and show less inhibition towards this subgroup than towards the dizinc members of B1 and B3) or are inactivators behaving as substrates for the dizinc family members. The present work reveals that certain pyridine carboxylates are competitive inhibitors of CphA, a subclass B2 enzyme. X-ray crystallographic analyses demonstrate that pyridine-2,4-dicarboxylic acid chelates the zinc ion in a bidentate manner within the active site. Salts of these compounds are already available and undergoing biomedical testing for various nonrelated purposes. Pyridine carboxylates appear to be useful templates for the development of more-complex, selective, nontoxic inhibitors of subclass B2 metallo-beta-lactamases. [less ▲]

Detailed reference viewed: 16 (1 ULg)
Full Text
Peer Reviewed
See detailProbing the specificity of the subclass B3 FEZ-1 metallo-beta-lactamase by site-directed mutagenesis
Mercuri, P. S.; Garcia-Saez, I.; De Vriendt, K. et al

in Journal of Biological Chemistry (2004), 279(32), 33630-33638

The subclass B3 FEZ-1 beta-lactamase produced by Fluoribacter (Legionella) gormanii is a Zn(II)-containing enzyme that hydrolyzes the beta-lactam bond in penicillins, cephalosporins, and carbapenems. FEZ ... [more ▼]

The subclass B3 FEZ-1 beta-lactamase produced by Fluoribacter (Legionella) gormanii is a Zn(II)-containing enzyme that hydrolyzes the beta-lactam bond in penicillins, cephalosporins, and carbapenems. FEZ-1 has been extensively studied using kinetic, computational modeling and x-ray crystallography. In an effort to probe residues potentially involved in substrate binding and zinc binding, five site-directed mutants of FEZ-1 (H121A, Y156A, S221A, N225A, and Y228A) were prepared and characterized using metal analyses and steady state kinetics. The activity of H121A is dependent on zinc ion concentration. The H121A monozinc form is less active than the dizinc form, which exhibits an activity similar to that of the wild type enzyme. Tyr156 is not essential for binding and hydrolysis of the substrate. Substitution of residues Ser221 and Asn225 modifies the substrate profile by selectively decreasing the activity against carbapenems. The Y228A mutant is inhibited by the product formed upon hydrolysis of cephalosporins. A covalent bond between the side chain of Cys200 and the hydrolyzed cephalosporins leads to the formation of an inactive and stable complex. [less ▲]

Detailed reference viewed: 9 (0 ULg)
Full Text
Peer Reviewed
See detailUpdate of the standard numbering scheme for class B beta-lactamases
Garau, G.; Garcia-Saez, I.; Bebrone, Carine ULg et al

in Antimicrobial Agents and Chemotherapy (2004), 48(7), 2347-2349

Detailed reference viewed: 25 (2 ULg)
Full Text
Peer Reviewed
See detailThe 1.5-angstrom structure of Chryseobacterium meningosepticum zinc beta-lactamase in complex with the inhibitor, D-captopril
Garcia-Saez, I.; Hopkins, J.; Papamicael, C. et al

in Journal of Biological Chemistry (2003), 278(26), 23868-23873

The crystal structure of the class-B beta-lactamase, BlaB, from the pathogenic bacterium, Chryseobacterium meningosepticum, in complex with the inhibitor, D-captopril, has been solved at 1.5-Angstrom ... [more ▼]

The crystal structure of the class-B beta-lactamase, BlaB, from the pathogenic bacterium, Chryseobacterium meningosepticum, in complex with the inhibitor, D-captopril, has been solved at 1.5-Angstrom resolution. The enzyme has the typical alphabeta/betaalpha metallo-beta-lactamase fold and the characteristic two metal binding sites of members of the subclass B1, in which two Zn2+ ions were identified. D-Captopril, a diastereoisomer of the commercial drug, captopril, acts as an inhibitor by displacing the catalytic hydroxyl ion required for antibiotic hydrolysis and intercalating its sulfhydryl group between the two Zn2+ ions. Interestingly, D-captopril is located on one side of the active site cleft. The x-ray structure of the complex of the closely related enzyme, IMP-1, with a mercaptocarboxylate inhibitor, which also contains a sulfhydryl group bound to the two Zn2+ ions, shows the ligand to be located on the opposite side of the active site cleft. A molecule generated by fusion of these two inhibitors would cover the entire cleft, suggesting an interesting approach to the design of highly specific inhibitors. [less ▲]

Detailed reference viewed: 158 (0 ULg)
Full Text
Peer Reviewed
See detailThree-dimensional structure of FEZ-1, a monomeric subclass B3 metallo-beta-lactamase from Fluoribacter gormanii, in native form and in complex with D-captopril
Garcia-Saez, I.; Mercuri, P. S.; Papamicael, C. et al

in Journal of Molecular Biology (2003), 325(4), 651-660

The beta-lactamases are involved in bacterial resistance to penicillin and related compounds. Members of the metallo-enzyme class are now found in many pathogenic bacteria and are thus becoming of major ... [more ▼]

The beta-lactamases are involved in bacterial resistance to penicillin and related compounds. Members of the metallo-enzyme class are now found in many pathogenic bacteria and are thus becoming of major clinical importance. The structures of the Zn-beta-lactamase from Fluoribacter gormanii (FEZ-1) in the native and in the complex form are reported here. FEZ-I is a monomeric enzyme, which possesses two zinc-binding sites. These structures are discussed in comparison with those of the tetrameric L1 enzyme produced by Stenotrophomonas maltophilia. From this analysis, amino acids involved in the oligomerization of L1 are clearly identified. Despite the similarity in fold, the active site of FEZ-1 was found to be significantly different. Two residues, which were previously implicated in function, are not present in L1 or in FEZ-1. The broad-spectrum substrate profile of Zn-beta-lactamases arises from the rather wide active-site cleft, where various P-lactam compounds can be accommodated. (C) 2003 Elsevier Science Ltd. All rights reserved. [less ▲]

Detailed reference viewed: 10 (0 ULg)
Full Text
Peer Reviewed
See detailStandard Numbering Scheme for Class B Beta-Lactamases
Galleni, Moreno ULg; Lamotte-Brasseur, J.; Rossolini, G. M. et al

in Antimicrobial Agents and Chemotherapy (2001), 45(3), 660-3

Detailed reference viewed: 12 (0 ULg)
Full Text
Peer Reviewed
See detailStructural effects of the active site mutation cysteine to serine in Bacillus cereus zinc-beta-lactamase.
Chantalat, L.; Duee, E.; Galleni, Moreno ULg et al

in Protein science : a publication of the Protein Society (2000), 9(7), 1402-6

Beta-lactamases are involved in bacterial resistance. Members of the metallo-enzyme class are now found in many pathogenic bacteria and are becoming thus of major clinical importance. Despite the ... [more ▼]

Beta-lactamases are involved in bacterial resistance. Members of the metallo-enzyme class are now found in many pathogenic bacteria and are becoming thus of major clinical importance. Despite the availability of Zn-beta-lactamase X-ray structures their mechanism of action is still unclear. One puzzling observation is the presence of one or two zincs in the active site. To aid in assessing the role of zinc content in beta-lactam hydrolysis, the replacement by Ser of the zinc-liganding residue Cys168 in the Zn-beta-lactamase from Bacillus cereus strain 569/H/9 was carried out: the mutant enzyme (C168S) is inactive in the mono-Zn form, but active in the di-Zn form. The structure of the mono-Zn form of the C168S mutant has been determined at 1.85 A resolution. Ser168 occupies the same position as Cys168 in the wild-type enzyme. The protein residues mostly affected by the mutation are Asp90-Arg91 and His210. A critical factor for the activity of the mono-Zn species is the distance between Asp90 and the Zn ion, which is controlled by Arg91: a slight movement of Asp90 impairs catalysis. The evolution of a large superfamily including Zn-beta-lactamases suggests that they may not all share the same mechanism. [less ▲]

Detailed reference viewed: 11 (0 ULg)
Full Text
Peer Reviewed
See detailPreference of Cd(II) and Zn(II) for the two metal sites in Bacillus cereus beta-lactamase II: A perturbed angular correlation of gamma-rays spectroscopic study.
Paul-Soto, R.; Zeppezauer, M.; Adolph, H. W. et al

in Biochemistry (1999), 38(50), 16500-6

Cd-substituted forms of the Bacillus cereus metallo-beta-lactamases (BCII) were studied by perturbed angular correlation of gamma-rays (PAC) spectroscopy. At very low [Cd]:[apo-beta-lactamase] ratios, two ... [more ▼]

Cd-substituted forms of the Bacillus cereus metallo-beta-lactamases (BCII) were studied by perturbed angular correlation of gamma-rays (PAC) spectroscopy. At very low [Cd]:[apo-beta-lactamase] ratios, two nuclear quadrupole interactions (NQI) were detected. For [Cd]:[apo-beta-lactamase] ratios between 0.8 and 3.0, two new NQIs appear, and the spectra show that up to 2 cadmium ions can be bound per molecule of apoenzyme. These results show the existence of two interacting Cd-binding sites in BCII. The relative populations of the two NQIs found at low [Cd]:[apo-beta-lactamase] ratios yielded a 1:3 ratio for the microscopic dissociation constants of the two different metal sites (when only one cadmium ion is bound). X-ray diffraction data at pH 7.5 demonstrate that also for Zn(II) two binding sites exist, which may be bridged by a solvent molecule. The measured NQIs could be assigned to the site with three histidines as metal ligands (three-His site) and to the site with histidine, cysteine, and aspartic acid as metal ligands (Cys site), respectively, by PAC measurements on the Cys168Ala mutant enzyme. This assignment shows that cadmium ions preferentially bind to the Cys site. This is in contrast to the preference of Zn(II) in the hybrid Zn(II)Cd(II) enzyme, where an analysis of the corresponding PAC spectrum showed that Cd(II) occupied the Cys site, whereby Zn(II) occupied the site with three histidines. The difference between Zn(II) and Cd(II) in affinity for the two sites is combined with the kinetics of hydrolysis of nitrocefin for different metal ion substitutions (Zn(2)E, ZnE, Cd(2)E, CdE, and ZnCdE) to study the function of the two metal ion binding sites. [less ▲]

Detailed reference viewed: 50 (0 ULg)
Peer Reviewed
See detailX-ray structure of the ZnII beta-lactamase from Bacteroides fragilis in an orthorhombic crystal form.
Carfi, A.; Duee, E.; Paul-Soto, R. et al

in Acta crystallographica. Section D, Biological crystallography (1998), 54(Pt 1), 45-57

beta-Lactamases are extracellular or periplasmic bacterial enzymes which confer resistance to beta-lactam antibiotics. On the basis of their catalytic mechanisms, they can be divided into two major groups ... [more ▼]

beta-Lactamases are extracellular or periplasmic bacterial enzymes which confer resistance to beta-lactam antibiotics. On the basis of their catalytic mechanisms, they can be divided into two major groups: active-site serine enzymes (classes A, C and D) and the ZnII enzymes (class B). The first crystal structure of a class B enzyme, the metallo-beta-lactamase from Bacillus cereus, has been solved at 2.5 A resolution [Carfi, Pares, Duee, Galleni, Duez, Frere & Dideberg (1995). EMBO J. 14, 4914-4921]. Recently, the crystal structure of the metallo-beta-lactamase from Bacteroides fragilis has been determined in a tetragonal space group [Concha, Rasmussen, Bush & Herzberg (1996). Structure, 4, 823-836]. The structure of the metallo-beta-lactamase from B. fragilis in an orthorhombic crystal form at 2.0 A resolution is reported here. The final crystallographic R is 0.196 for all the 32501 observed reflections in the range 10-2.0 A. The refined model includes 458 residues, 437 water molecules, four zinc and two sodium ions. These structures are discussed with reference to Zn binding and activity. A catalytic mechanism is proposed which is coherent with metallo-beta-lactamases being active with either one Zn ion (as in Aeromonas hydrophila) or two Zn ions (as in B. fragilis) bound to the protein. [less ▲]

Detailed reference viewed: 15 (0 ULg)
Peer Reviewed
See detailThe structures and catalytic mechanisms of active-site serine beta-lactamases.
Lamotte, Josette ULg; Knox, J.; Kelly, J. A. et al

in Biotechnology & Genetic Engineering Reviews (1994), 12

Detailed reference viewed: 25 (0 ULg)
Full Text
Peer Reviewed
See detailCrystallization of a genetically engineered water-soluble primary penicillin target enzyme. The high molecular mass PBP2x of Streptococcus pneumoniae.
Charlier, Paulette ULg; Buisson, G.; Dideberg, O. et al

in Journal of Molecular Biology (1993), 232(3), 1007-9

A genetically engineered water-soluble derivative of PBP2x of Streptococcus pneumoniae has been produced, purified and crystallized in a form suitable for X-ray diffraction analysis. The best crystals ... [more ▼]

A genetically engineered water-soluble derivative of PBP2x of Streptococcus pneumoniae has been produced, purified and crystallized in a form suitable for X-ray diffraction analysis. The best crystals have been grown at 15 degrees C, from solutions containing 8% polyethylene glycol 10,000 at pH values ranging from 3.9 to 6.0. These crystals diffract to a resolution of 3.5 A and have a space group P6(1)22 (or enantiomorph) with unit cell dimensions of a = b = 162.2 A, c = 171.8 A, alpha = beta = 90 degrees, gamma = 120 degrees. The molecular mass and cell dimensions suggest that there is one molecule of enzyme per asymmetric unit. The breakdown of a chromogenic cephalosporin derivative diffused into a crystal reveals clearly that the enzyme is active in the crystalline state. [less ▲]

Detailed reference viewed: 55 (0 ULg)
Peer Reviewed
See detailStructure du 8-chloro-11-(méthylpipérazin-1-yl)dibenzo[b,f]-1,4-thiazépine
Dupont, L.; Dideberg, O.; Liégeois, Jean-François ULg et al

in Acta Crystallographica Section C-Crystal Structure Communications (1992), C48

Detailed reference viewed: 9 (0 ULg)
Peer Reviewed
See detailStructure du 6-(4-méthylpipérazin-1-yl)-11H-pyrido[2,3-b][1,4]benzodiazépine 1,5-hydrate
Dupont, L.; Englebert, S.; Dideberg, O. et al

in Acta Crystallographica Section C-Crystal Structure Communications (1992), C48

Detailed reference viewed: 7 (4 ULg)
Full Text
Peer Reviewed
See detailComparison of the Sequences of Class a β-lactamase and of the Secondary Structure Elements of Penicillin-Recognizing Proteins
Joris, Bernard ULg; Ledent, P.; Dideberg, O. et al

in Antimicrobial Agents and Chemotherapy (1991), 35(11), 2294-2301

The sequences of class A beta-lactamases were compared. Four main groups of enzymes were distinguished: those from the gram-negative organisms and bacilli and two distinct groups of Streptomyces spp. The ... [more ▼]

The sequences of class A beta-lactamases were compared. Four main groups of enzymes were distinguished: those from the gram-negative organisms and bacilli and two distinct groups of Streptomyces spp. The Staphylococcus aureus PC1 enzyme, although somewhat closer to the enzyme from the Bacillus group, did not belong to any of the groups of beta-lactamases. The similarities between the secondary structure elements of these enzymes and those of the class C beta-lactamases and of the Streptomyces sp. strain R61 DD-peptidase were also analyzed and tentatively extended to the class D beta-lactamases. A unified nomenclature of secondary structure elements is proposed for all the penicillin-recognizing enzymes. [less ▲]

Detailed reference viewed: 22 (3 ULg)
Peer Reviewed
See detailStructures du 11-formyl-5-(4-méthylpipérazin-1-yl)-11H-pyrido[2,3b][1,5]benzodiazépine et du 6-(4-méthylpipérazin-1-yl)-11-méthyl-11H-pyrido[2,3-b][1,4]benzodiazépine
Dupont, L.; Englebert, S.; Dideberg, O. et al

in Acta Crystallographica Section C-Crystal Structure Communications (1991), C47

Detailed reference viewed: 12 (0 ULg)
Peer Reviewed
See detailStructure du méthyl-4 pipérazinyl-1)-10 pyrido[4,3-b][1,4]benzothiazépine
Dupont, L.; Dideberg, O.; Liégeois, Jean-François ULg et al

in Acta Crystallographica Section C-Crystal Structure Communications (1991), C47

Detailed reference viewed: 6 (0 ULg)
Full Text
Peer Reviewed
See detailStructure de la bétaïne du carboxyméthyl-1 méthylamino-4 triazolium-1,2,4
Dupont, L.; Englebert, S.; Dideberg, O. et al

in Acta Crystallographica (1991), C47

Detailed reference viewed: 14 (1 ULg)
Full Text
Peer Reviewed
See detailStructure de l'acide (tert-butylamino-4 oxo-5 triazol-1,2,4 yle-1)acétique
Dupont, L.; Englebert, S.; Dideberg, O. et al

in Acta Crystallographica (1991), C47

Detailed reference viewed: 7 (0 ULg)
Full Text
Peer Reviewed
See detailStructures du cyclohexyl-1[(cycloheptylamino-4 pyridyl-3)sulfonyl]-3 urée et de l'hydrogénonitrate du cyclohexyl-1[(cyclooctylamino-4 pyridyl-3)sulfonyl]-3 urée
Dupont, L.; Dideberg, O.; Masereel, B. et al

in Acta Crystallographica (1991), C47

Detailed reference viewed: 4 (0 ULg)
Full Text
Peer Reviewed
See detailStructure du [4-phénylacétylimino-1-(1,2,4-triazolio)]acétate de sodium dihydrate
Dupont, L.; Englebert, S.; Dideberg, O. et al

in Acta Crystallographica (1991), C47

Detailed reference viewed: 7 (0 ULg)