Browsing
     by title


0-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

or enter first few letters:   
OK
Peer Reviewed
See detailMutational analysis of the p50 subunit of NF-kappa B and inhibition of NF-kappa B activity by trans-dominant p50 mutants.
Bressler, P.; Brown, K.; Timmer, W. et al

in Journal of Virology (1993), 67(1), 288-93

The NF-kappa B family of DNA-binding proteins regulates the expression of many cellular and viral genes. Each of these proteins has an N-terminal region that is homologous to the c-Rel proto-oncogene ... [more ▼]

The NF-kappa B family of DNA-binding proteins regulates the expression of many cellular and viral genes. Each of these proteins has an N-terminal region that is homologous to the c-Rel proto-oncogene product, and this Rel homology region defines both DNA binding and protein dimerization properties of the individual proteins. Most of the NF-kappa B family members have been shown to associate with themselves or with each other to form homodimers or heterodimers, and previous studies have shown that dimerization of NF-kappa B factors is necessary to provide a functional DNA binding domain. We have used site-directed mutagenesis to identify regions in the Rel homology domain of the p50/NF-kappa B protein that are important for DNA binding and protein dimerization. Our studies have identified mutations of p50 that interfere with DNA binding only and those that interfere with protein dimerization. Mutations of p50 which disrupt only DNA binding were still able to associate with other members of the NF-kappa B protein family. We demonstrate that such heterodimeric complexes inhibit transcriptional activation mediated in trans through a cis-acting kappa B motif; therefore, we have identified trans-dominant negative mutants of p50. [less ▲]

Detailed reference viewed: 2 (0 ULg)
Full Text
Peer Reviewed
See detailMutational Analysis Of The Tre2 Oncogene Encoding An Inactive Rabgap
Bizimungu, C.; Thomas, Annick ULg; Brasseur, Robert ULg et al

in Biotechnology Letters (2007), 29(12), 1927-37

The TRE2 oncoprotein is structurally related to the RabGAP (GTPase-activating protein) family. However, TRE2 seems enzymatically inactive. Two regions are important for its lack of GAP activity. First ... [more ▼]

The TRE2 oncoprotein is structurally related to the RabGAP (GTPase-activating protein) family. However, TRE2 seems enzymatically inactive. Two regions are important for its lack of GAP activity. First, the TBC domain, forming the catalytically active domain of RabGAPs, is non-functional in the oncoprotein. Also involved in TRE2 inactivity is the 93-aa region flanking the TBC domain on the C-terminal side. In order to identify the residues responsible for non-functionality, we performed hydrophobic cluster analysis of the oncoprotein sequence, combined with secondary structure prediction, receptor-binding domain analysis, and a tilted peptide calculation. These analyses were complemented with site-directed and random mutagenesis experiments. On the basis of our data, we hypothesize that the lack of secondary structure of the region flanking the TBC domain in TRE2 may explain why this region plays a role in the lack of GAP activity, even when a potentially functional TBC domain is present. [less ▲]

Detailed reference viewed: 8 (1 ULg)
Full Text
Peer Reviewed
See detailMutational analysis of the two zinc-binding sites of the Bacillus cereus 569/H/9 metallo-beta-lactamase
De Seny, Dominique ULg; Prosperi, Christelle ULg; Bebrone, Carine ULg et al

in Biochemical Journal (2002), 363(Pt 3), 687-696

The metallo-beta-lactamase BcII from Bacillus cereus 569/H/9 possesses a binuclear zinc centre. The mono-zinc form of the enzyme displays an appreciably high activity. although full efficiency is observed ... [more ▼]

The metallo-beta-lactamase BcII from Bacillus cereus 569/H/9 possesses a binuclear zinc centre. The mono-zinc form of the enzyme displays an appreciably high activity. although full efficiency is observed for the di-zinc enzyme. In an attempt to assign the involvement of the different zinc ligands in the catalytic properties of BcII, individual substitutions of selected amino acids were generated. With the exception of His(116) --> Ser (H116S), C221A and C221S, the mono- and di-zinc forms of all the other mutants were poorly active. The activity of H116S decreases by a factor of 10 when compared with the wild type. The catalytic efficiency of C221A and C221S was zinc-dependent. The monozinc forms of these mutants exhibited a low activity, whereas the catalytic efficiency of their respective di-zinc forms was comparable with that of the wild type. Surprisingly, the zinc contents of the mutants and the wild-type Bell were similar. These data suggest that the affinity of the beta-lactamase for the metal was not affected by the substitution of the ligand. The pH-dependence of the H196S catalytic efficiency indicates that the zinc ions participate in the hydrolysis of the beta-lactam ring by acting as a Lewis acid. The zinc ions activate the catalytic water molecule, but also polarize the carbonyl bond of the beta-lactam ring and stabilize the development of a negative charge on the carbonyl oxygen of the tetrahedral reaction intermediate. Our studies also demonstrate that Asn(233) is not directly involved in the interaction with the substrates. [less ▲]

Detailed reference viewed: 31 (8 ULg)
Full Text
Peer Reviewed
See detailMutational analysis of the zinc- and substrate-binding sites in the CphA metallo-beta-lactamase from Aeromonas hydrophila.
Bebrone, Carine ULg; Anne, Christine; Kerff, Frédéric ULg et al

in Biochemical Journal (2008), 414(1), 151-9

The subclass B2 CphA (Carbapenemase hydrolysing Aeromonas) beta-lactamase from Aeromonas hydrophila is a Zn(2+)-containing enzyme that specifically hydrolyses carbapenems. In an effort to evaluate ... [more ▼]

The subclass B2 CphA (Carbapenemase hydrolysing Aeromonas) beta-lactamase from Aeromonas hydrophila is a Zn(2+)-containing enzyme that specifically hydrolyses carbapenems. In an effort to evaluate residues potentially involved in metal binding and/or catalysis (His(118), Asp(120), His(196) and His(263)) and in substrate specificity (Val(67), Thr(157), Lys(224) and Lys(226)), site-directed mutants of CphA were generated and characterized. Our results confirm that the first zinc ion is in interaction with Asp(120) and His(263), and thus is located in the 'cysteine' zinc-binding site. His(118) and His(196) residues seem to be interacting with the second zinc ion, as their replacement by alanine residues has a negative effect on the affinity for this second metal ion. Val(67) plays a significant role in the binding of biapenem and benzylpenicillin. The properties of a mutant with a five residue (LFKHV) insertion just after Val(67) also reveals the importance of this region for substrate binding. This latter mutant has a higher affinity for the second zinc ion than wild-type CphA. The T157A mutant exhibits a significantly modified activity spectrum. Analysis of the K224Q and N116H/N220G/K224Q mutants suggests a significant role for Lys(224) in the binding of substrate. Lys(226) is not essential for the binding and hydrolysis of substrates. Thus the present paper helps to elucidate the position of the second zinc ion, which was controversial, and to identify residues important for substrate binding. [less ▲]

Detailed reference viewed: 35 (7 ULg)
Full Text
Peer Reviewed
See detailMutational analysis of varicella-zoster virus major immediate-early protein IE62
Baudoux, Laurence; Defechereux, Patricia; Schoonbroodt, Sonia et al

in Nucleic Acids Research (1995), 23(8), 1341-1349

The varicella-zoster virus (VZV) open reading frame 62 encodes an immediate-early protein (IE62) that transactivates expression of various VZV promoters and autoregulates its own expression in transient ... [more ▼]

The varicella-zoster virus (VZV) open reading frame 62 encodes an immediate-early protein (IE62) that transactivates expression of various VZV promoters and autoregulates its own expression in transient expression assays. In Vero cells, IE62 was shown to transactivate the expression of all putative immediate-early (IE) and early (E) genes of VZV with an up-regulating effect at low intracellular concentrations. To define the functional domains involved in the regulatory properties of IE62, a large number of in-frame insertions and deletions were introduced into a plasmid-borne copy of the gene encoding IE62. Studies of the regulatory activities of the resultant mutant polypeptides in transient expression assays allowed to delineate protein regions important for repression of its own promoter and for transactivation of a VZV putative immediate-early gene (ORF61) promoter and an early gene (ORF29) promoter. This mutational analysis resulted in the identification of a new functional domain situated at the border between regions 4 and 5 which plays a crucial role in the IE62 regulatory functions. This domain turned out to be very well conserved amongst homologous alphaherpesvirus regulatory proteins and appeared to be rich in bulky hydrophobic and proline residues, similar to the proline-rich region of the CAAT box binding protein CTF-1. By immunofluorescence, a nuclear localization signal has been mapped in region 3. [less ▲]

Detailed reference viewed: 16 (1 ULg)
Full Text
Peer Reviewed
See detailMutational analysis of VIM-2 reveals an essential determinant for metallo-beta-lactamase stability and folding.
Borgianni, Luisa; Vandenameele, Julie ULg; Matagne, André ULg et al

in Antimicrobial Agents and Chemotherapy (2010), 54(8), 3197-204

Metallo-beta-lactamase (MBL)-producing bacteria are emerging worldwide and represent a formidable threat to the efficacy of relevant beta-lactams, including carbapenems, expanded-spectrum cephalosporins ... [more ▼]

Metallo-beta-lactamase (MBL)-producing bacteria are emerging worldwide and represent a formidable threat to the efficacy of relevant beta-lactams, including carbapenems, expanded-spectrum cephalosporins, and beta-lactamase inactivator/beta-lactam combinations. VIM-2 is currently the most widespread MBL and represents a primary target for MBL inhibitor research, the clinical need for which is expected to further increase in the future. Using a saturation mutagenesis approach, we probed the importance of four residues (Phe-61, Ala-64, Tyr-67, and Trp-87) located close to the VIM-2 active site and putatively relevant to the enzyme activity based on structural knowledge of the enzyme and on structure-activity relationships of the subclass B1 MBLs. The ampicillin MIC values shown by the various mutants were affected very differently depending on the randomized amino acid position. Position 64 appeared to be rather tolerant to substitution, and kinetic studies showed that the A64W mutation did not significantly affect substrate hydrolysis or binding, representing an important difference from IMP-type enzymes. Phe-61 and Tyr-67 could be replaced with several amino acids without the ampicillin MIC being significantly affected, but in contrast, Trp-87 was found to be critical for ampicillin resistance. Further kinetic and biochemical analyses of W87A and W87F variants showed that this residue is apparently important for the structure and proper folding of the enzyme but, surprisingly, not for its catalytic activity. These data support the critical role of residue 87 in the stability and folding of VIM-2 and might have strong implications for MBL inhibitor design, as this residue would represent an ideal target for interaction with small molecules. [less ▲]

Detailed reference viewed: 25 (3 ULg)
Full Text
Peer Reviewed
See detailMutations Affecting the Mitochondrial Genes Encoding the Cytochrome Oxidase Subunit I and Apocytochrome B of Chlamydomonas Reinhardtii
Colin, Martine ULg; Dorthu, M. P.; Duby, Franceline ULg et al

in Molecular & General Genetics [=MGG] (1995), 249(2), 179-84

Mitochondrial mutants of the green alga Chlamydomonas reinhardtii that are inactivated in the cytochrome pathway of respiration have previously been isolated. Despite the fact that the alternative oxidase ... [more ▼]

Mitochondrial mutants of the green alga Chlamydomonas reinhardtii that are inactivated in the cytochrome pathway of respiration have previously been isolated. Despite the fact that the alternative oxidase pathway is still active the mutants have lost the capacity to grow heterotrophically (dark + acetate) and display reduced growth under mixotrophic conditions (light + acetate). In crosses between wild-type and mutant cells, the meiotic progeny only inherit the character transmitted by the mt- parent, which indicates that the mutations are located in the 15.8 kb linear mitochondrial genome. Two new mutants (dum-18 and dum-19) have now been isolated and characterized genetically, biochemically and at the molecular level. In addition, two previously isolated mutants (dum-11 and dum-15) were characterized in more detail. dum-11 contains two types of deleted mitochondrial DNA molecules: 15.1 kb monomers lacking the subterminal part of the genome, downstream of codon 147 of the apocytochrome b (COB) gene, and dimers resulting from head-to-head fusion of asymmetrically deleted monomers (15.1 and 9.5 kb DNA molecules, respectively). As in the wild type, the three other mutants contain only 15.8 kb mitochondrial DNA molecules. dum-15 is mutated at codon 140 of the COB gene, a serine (TCT) being changed into a tyrosine (TAC). dum-18 and dum-19 both inactivate cytochrome c oxidase, as a result of frameshift mutations (addition or deletion of 1 bp) at codons 145 and 152, respectively, of the COX1 gene encoding subunit I of cytochrome c oxidase. In a total of ten respiratory deficient mitochondrial mutants characterized thus far, only mutations located in COB or COX1 have been isolated.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]

Detailed reference viewed: 29 (4 ULg)
Full Text
Peer Reviewed
See detailMutations AIP chez les jeunes patients en dessous de 30 ans avec adénome hypophysaire agressif
Beckers, Albert ULg; Tichomirowa, M.; Barlier, A. et al

in Annales d'Endocrinologie (2010, September), 71(5), 397

Detailed reference viewed: 20 (4 ULg)
Full Text
See detailMutations AIP chez les jeunes patients en-dessous de 30 ans avec adénome hypophysaire agressif
Beckers, Albert ULg; Tichomirowa, M.; Barlier, A. et al

in 27ème Congrès de la Société Française d'Endocrinologie - Deauville, 29 septembre - 2 octobre 2010 (2010, September)

Detailed reference viewed: 25 (4 ULg)
Full Text
See detailMutations des localisations des services et mutations urbaines. Questionnements et perspectives
Merenne-Schoumaker, Bernadette ULg

in Revista de Geografia, Universidade Federal de Pernambuco (2002), 17(2), 41-56

The aim of this paper is to analyse the relationships between urban mutations and service locations. Work is developed in four times: facts, causes, consequences and prospects. Without doubt, the spatial ... [more ▼]

The aim of this paper is to analyse the relationships between urban mutations and service locations. Work is developed in four times: facts, causes, consequences and prospects. Without doubt, the spatial transfers of service activities can be considered as both, a cause and a consequence of urban sprawl. It is related to the release of mobility constraints, to the specific changes that affected many economic activities, and also to the new behaviours of many actors (customers/ visitors, property developers and public authorities). As this evolution is incompatible with the objectives of sustainable urban development, several action possibilities can be proposed: new management of the daily mobilities, reduction in space consumption and new governance. [less ▲]

Detailed reference viewed: 53 (1 ULg)
See detailLes mutations du mouvement associatif “immigré” en Belgique
Martiniello, Marco ULg

Scientific conference (1996, April 01)

Detailed reference viewed: 5 (0 ULg)
Full Text
Peer Reviewed
See detailMutations in FKBP10 cause recessive osteogenesis imperfecta and bruck syndrome.
Kelley, B. P.; Malfait, F.; Bonafe, L. et al

in Journal of Bone and Mineral Research (2011)

Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue characterized by bone fragility and alteration in synthesis and post-translational modification of type I collagen. Autosomal ... [more ▼]

Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue characterized by bone fragility and alteration in synthesis and post-translational modification of type I collagen. Autosomal dominant OI is caused by mutations in the genes (COL1A1 or COL1A2) encoding the chains of type I collagen. Bruck syndrome is a recessive disorder featuring congenital contractures in addition to bone fragility; Bruck syndrome type 2 is caused by mutations in PLOD2 encoding collagen lysyl hydroxylase, while Bruck Syndrome type 1 has been mapped to 17q12 but the gene has remained elusive so far. Recently, the molecular spectrum of OI has been expanded with the description of the basis of a unique post-translational modification of type I procollagen, i.e. 3-prolyl-hydroxylation. Three proteins, cartilage-associated protein (CRTAP), prolyl-3-hydroxylase-1 (P3H1, encoded by the LEPRE1 gene), and the prolyl cis-trans isomerase cyclophilin-B (PPIB) form a complex that is required for fibrillar collagen 3-prolyl-hydroxylation and mutations in each gene have been shown to cause recessive forms of OI. Since then, an additional putative collagen chaperone complex, composed of FKBP10 (also known as FKBP65) and SERPINH1 (also known as HSP47), has also been shown to be mutated in recessive OI. Here, we describe five families with OI-like bone fragility in association with congenital contractures who all had FKBP10 mutations. Given the previous mapping of Bruck syndrome type 1 to the chromosomal region containing FKBP10, we conclude that FKBP10 mutations are the cause of Bruck syndrome type 1. (c) 2010 American Society for Bone and Mineral Research. [less ▲]

Detailed reference viewed: 25 (5 ULg)
Full Text
Peer Reviewed
See detailMutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes.
Endele, Sabine; Rosenberger, Georg; Geider, Kirsten et al

in Nature Genetics (2010), 42(11), 1021-6

N-methyl-D-aspartate (NMDA) receptors mediate excitatory neurotransmission in the mammalian brain. Two glycine-binding NR1 subunits and two glutamate-binding NR2 subunits each form highly Ca(2 ... [more ▼]

N-methyl-D-aspartate (NMDA) receptors mediate excitatory neurotransmission in the mammalian brain. Two glycine-binding NR1 subunits and two glutamate-binding NR2 subunits each form highly Ca(2)(+)-permeable cation channels which are blocked by extracellular Mg(2)(+) in a voltage-dependent manner. Either GRIN2B or GRIN2A, encoding the NMDA receptor subunits NR2B and NR2A, was found to be disrupted by chromosome translocation breakpoints in individuals with mental retardation and/or epilepsy. Sequencing of GRIN2B in 468 individuals with mental retardation revealed four de novo mutations: a frameshift, a missense and two splice-site mutations. In another cohort of 127 individuals with idiopathic epilepsy and/or mental retardation, we discovered a GRIN2A nonsense mutation in a three-generation family. In a girl with early-onset epileptic encephalopathy, we identified the de novo GRIN2A mutation c.1845C>A predicting the amino acid substitution p.N615K. Analysis of NR1-NR2A(N615K) (NR2A subunit with the p.N615K alteration) receptor currents revealed a loss of the Mg(2)(+) block and a decrease in Ca(2)(+) permeability. Our findings suggest that disturbances in the neuronal electrophysiological balance during development result in variable neurological phenotypes depending on which NR2 subunit of NMDA receptors is affected. [less ▲]

Detailed reference viewed: 14 (1 ULg)
Full Text
Peer Reviewed
See detailMutations in PYCR1 cause cutis laxa with progeroid features.
Reversade, Bruno; Escande-Beillard, Nathalie; Dimopoulou, Aikaterini et al

in Nature Genetics (2009), 41(9), 1016-21

Autosomal recessive cutis laxa (ARCL) describes a group of syndromal disorders that are often associated with a progeroid appearance, lax and wrinkled skin, osteopenia and mental retardation. Homozygosity ... [more ▼]

Autosomal recessive cutis laxa (ARCL) describes a group of syndromal disorders that are often associated with a progeroid appearance, lax and wrinkled skin, osteopenia and mental retardation. Homozygosity mapping in several kindreds with ARCL identified a candidate region on chromosome 17q25. By high-throughput sequencing of the entire candidate region, we detected disease-causing mutations in the gene PYCR1. We found that the gene product, an enzyme involved in proline metabolism, localizes to mitochondria. Altered mitochondrial morphology, membrane potential and increased apoptosis rate upon oxidative stress were evident in fibroblasts from affected individuals. Knockdown of the orthologous genes in Xenopus and zebrafish led to epidermal hypoplasia and blistering that was accompanied by a massive increase of apoptosis. Our findings link mutations in PYCR1 to altered mitochondrial function and progeroid changes in connective tissues. [less ▲]

Detailed reference viewed: 44 (3 ULg)
Full Text
Peer Reviewed
See detailMutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas.
Barlier, Anne; Vanbellinghen, Jean-François ULg; Daly, Adrian ULg et al

in Journal of Clinical Endocrinology and Metabolism (2007), 92(5), 1952-5

CONTEXT: Limited screening suggests that three germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are not involved in sporadic pituitary tumorigenesis. Multiple novel ... [more ▼]

CONTEXT: Limited screening suggests that three germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are not involved in sporadic pituitary tumorigenesis. Multiple novel mutations of this gene have since been identified in familial isolated pituitary adenoma cohorts. OBJECTIVE: The objective of the study was to undertake full AIP coding sequence screening to assess for the presence of germline and somatic mutations in European Union subjects with sporadic pituitary tumors. DESIGN: The study design was the analysis of DNA from peripheral blood lymphocytes and analysis of exons 1-6 and paraexonic intron sequences of AIP. Multiplex ligation-dependent probe amplification was used to screen separate sporadic pituitary tumor tissue samples for discrete and extensive deletions or mutations of the AIP gene. Setting: The study was conducted in university tertiary referral Clinical Genetics, Molecular Biology, and Endocrinology Departments. RESULTS: In 107 patients [prolactinomas (n =49), nonfunctioning tumors (n = 29), somatotropinomas (n = 26), ACTH-secreting tumors (n = 2), TSH-secreting tumors (n = 1)], no germline mutations of AIP were demonstrated. Among a group of 41 tumor samples from other subjects, a novel AIP mutation (R22X) was found in one sample in which the corresponding allele was deleted; follow-up screening of the patient demonstrated a germline R22X AIP mutation. CONCLUSIONS: AIP mutations do not appear to play a prominent role in sporadic pituitary tumorigenesis in this population of European subjects. [less ▲]

Detailed reference viewed: 24 (3 ULg)
Full Text
Peer Reviewed
See detailMutations In The Bovine Leukemia-Virus Tax Protein Can Abrogate The Long Terminal Repeat-Directed Transactivating Activity Without Concomitant Loss Of Transforming Potential
Willems, Luc ULg; Grimonpont, C.; Heremans, H. et al

in Proceedings of the National Academy of Sciences of the United States of America (1992), 89(9),

Detailed reference viewed: 11 (4 ULg)
Full Text
Peer Reviewed
See detailMutations in the ganglioside-induced differentiation-associated protein-1 (GDAP1) gene in intermediate type autosomal recessive Charcot-Marie-Tooth neuropathy
Senderek, J.; Bergmann, C.; RAMAEKERS, Vincent ULg et al

in Brain (2003), 126(3), 642-649

Mutations in the gene for the ganglioside-induced differentiation-associated protein-1 (GDAP1) on 8q21 recently were reported to cause autosomal recessive Charcot-Marie-Tooth (CMT) sensorimotor neuropathy ... [more ▼]

Mutations in the gene for the ganglioside-induced differentiation-associated protein-1 (GDAP1) on 8q21 recently were reported to cause autosomal recessive Charcot-Marie-Tooth (CMT) sensorimotor neuropathy. Neurophysiology and nerve pathology were heterogeneous in these cases: a subset of GDAP1 mutations was associated with peripheral nerve demyelination, whereas others resulted in axonal degeneration. In this study, we identified two novel mutations disrupting the GDAP1 reading frame. Homozygosity for a single base pair insertion in exon 3 (c.349_350insT) was observed in affected children from a Turkish inbred pedigree. The other novel allele detected in a German patient was a homozygous mutation of the intron 4 donor splice site (c.579 + 1G>A). Patients with GDAP1 mutations displayed severe, early childhood-onset CMT neuropathy with prominent pes equinovarus deformity and impairment of hand muscles. Nerve conduction velocities were between 25 and 35 m/s and peripheral nerve pathology showed axonal as well as demyelinating changes. These findings fitted the definition of intermediate type CMT and further support the view that GDAP1 is vital for both, axonal integrity and Schwann cell properties. [less ▲]

Detailed reference viewed: 1 (0 ULg)
Peer Reviewed
See detailMutations in the immunosuppressive peptide of bovine leukema virus affect fusion and infectivity in vivo
Gatot, Jean-Stéphane; Kettmann, Richard ULg; Callebaut-Mornon, Isabelle et al

in Virus Research (1997), 47(2-Special Issue), 103

Detailed reference viewed: 7 (0 ULg)