References of "De Lemos Esteves, Frédéric"
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See detailWhat do we know about the safety of corticosteroids in rheumatoid arthritis?
Ethgen, Olivier ULg; De Lemos Esteves, Frédéric ULg; Bruyère, Olivier ULg et al

in Current Medical Research & Opinion (2013), 29(9), 1147-60

Abstract Background: Clear information is still lacking on the safety of corticosteroids (GCs) therapy in RA despite six decades of clinical experience. Scope: We performed a literature search in Ovid ... [more ▼]

Abstract Background: Clear information is still lacking on the safety of corticosteroids (GCs) therapy in RA despite six decades of clinical experience. Scope: We performed a literature search in Ovid MEDLINE from January 2000 to December 2012. Our Population Intervention Comparator Outcomes (PICO) strategy search was: rheumatoid arthritis [Population], corticosteroids or glucocorticoids [Intervention], any comparison [Comparator], adverse effects [Outcome]. Studies were selected if they reported any measure of association between GCs intake and potential adverse effects in RA patients. Findings: We identified 1030 papers and selected for analysis 26 observational studies and six systematic reviews. The major side effects of GCs in RA are bone loss, risk of cardiovascular events and risk of infections as evidenced by large observational studies and not necessarily RCTs. Others associations were reported with herpes zoster, tuberculosis, hyperglycemia, cutaneous abnormalities, gastrointestinal perforation, respiratory infection and self-reported health problems such as cushingoid phenotype, ecchymosis, parchment-like skin, epistaxis, weight gain and sleep disturbance. Other potential adverse effects of GCs were studied but no association was found. These included psychological disorders, dermatophytosis, brain diseases, interstitial lung disease, memory deficit, metabolic syndrome, lymphoma, non-Hodgkin's lymphoma, renal function and cerebrovascular accidents. Most of the evidence emanates from observational researches and the inherent limitations of such data should be kept in mind. Conclusion: Recent observational data and systematic reviews suggest that GCs can lead to relatively alarming and burdensome side effects in RA. This is particularly true for patients who have longer term and higher dose therapies. GCs are largely used in RA and knowing their safety profile is essential to improve patients care. The design of new therapeutic strategies intended to minimize the daily dosing of GCs while conserving their beneficial effect should be encouraged. [less ▲]

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See detailAnalysis of Root Secreted Proteases in Arabidopsis thaliana and Nicotiana tabacum
Désiron, Carole ULg; De Lemos Esteves, Frédéric ULg; Natalis, Lucie et al

Poster (2011, June 09)

Plants are promising tools to produce complex recombinant proteins like antibodies. When host plants are grown on hydroponics, the production of recombinant proteins that are secreted by the roots ... [more ▼]

Plants are promising tools to produce complex recombinant proteins like antibodies. When host plants are grown on hydroponics, the production of recombinant proteins that are secreted by the roots ('rhizosecretion') greatly simplifies harvest and purification of the product, during whole plant life. However, proteases represent up to 10% of the naturally secreted proteins and are known to significantly decrease the yield of production by rhizosecretion. In this study, we analyzed the rhizosecreted proteases of Arabidopsis thaliana and Nicotiana tabacum. Total rhizosecreted proteins were recovered by salt extraction and the protease activity was assayed in vitro or by zymography. The relative contribution of major protease families to total activity was evaluated with specific inhibitors and revealed significant differences between the two species. The degradation capacity of the root-secreted proteases was further characterized against selected target proteins: BSA and human IgGs. [less ▲]

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See detailImproving the alkalophilic performances of the Xyl1 xylanase from Streptomyces sp S38: Structural comparison and mutational analysis
De Lemos Esteves, Frédéric ULg; Gouders, T.; Lamotte-Brasseur, J. et al

in Protein Science : A Publication of the Protein Society (2005), 14(2), 292-302

Endo-beta-1,4-xylanases of the family 11 glycosyl-hydrolases are catalytically active over a wide range of pH. Xyl1 from Streptomyces sp. S38 belongs to this family, and its optimum pH for enzymatic ... [more ▼]

Endo-beta-1,4-xylanases of the family 11 glycosyl-hydrolases are catalytically active over a wide range of pH. Xyl1 from Streptomyces sp. S38 belongs to this family, and its optimum pH for enzymatic activity is 6. Xyn11 from Bacillus agaradhaerens and XylJ from Bacillus sp. 41M-1 share 85% sequence identity and have been described as highly alkalophilic enzymes. In an attempt to better understand the alkalophilic adaptation of xylanases, the three-dimensional structures of Xyn11 and Xyl1 were compared. This comparison highlighted an increased number of salt-bridges and the presence of more charged residues in the catalytic cleft as well as an eight-residue-longer loop in the alkalophilic xylanase Xyn11. Some of these charges were introduced in the structure of Xyl1 by site-directed mutagenesis with substitutions Y16D, S18E, G50R, N92D, A135Q, E139K, and Y186E. Furthermore, the eight additional loop residues of Xyn11 were introduced in the homologous loop of Xyl1. In addition, the coding sequence of the XylJ catalytic domain was synthesized by recursive PCR, expressed in a Streptomyces host, purified, and characterized together with the Xyl1 mutants. The Y186E substitution inactivated Xyl1, but the activity was restored when this mutation was combined with the G50R or S18E substitutions. Interestingly, the E139K mutation raised the optimum pH of Xyl1 from 6 to 7.5 but had no effect when combined with the N92D substitution. Modeling studies identified the possible formation of an interaction between the introduced lysine and the substrate, which could be eliminated by the formation of a putative salt-bridge in the N92D/E139K mutant. [less ▲]

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See detailOn the way of understanding the adaptation to extreme pH of family 11 xylanases: Structural comparison and mutational analysis
De Lemos Esteves, Frédéric ULg; Ruelle, Virginie; Gouders, Thierry et al

Poster (2004, December)

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See detailAcidophilic adaptation of family 11 endo--1,4-xylanases: Modeling and mutational analysis
De Lemos Esteves, Frédéric ULg; Ruelle, Virginie; Lamotte-Brasseur, Josette ULg et al

in Protein Science : A Publication of the Protein Society (2004), 13(5), 12091218

Xyl1 from Streptomyces sp. S38 belongs to the low molecular mass family 11 of endo--1,4-xylanases. Its three-dimensional structure has been solved at 2.0 Å and its optimum temperature and pH for enzymatic ... [more ▼]

Xyl1 from Streptomyces sp. S38 belongs to the low molecular mass family 11 of endo--1,4-xylanases. Its three-dimensional structure has been solved at 2.0 Å and its optimum temperature and pH for enzymatic activity are 60°C and 6.0, respectively. Aspergillus kawachii xylanase XynC belongs to the same family but is an acidophilic enzyme with an optimum pH of 2.0. Structural comparison of Xyl1 and XynC showed differences in residues surrounding the two glutamic acid side chains involved in the catalysis that could be responsible for the acidophilic adaptation of XynC. Mutations W20Y, N48D, A134E, and Y193W were introduced by site-directed mutagenesis and combined in multiple mutants. Trp 20 and Tyr 193 are involved in substrate binding. The Y193W mutation inactivated Xyl1 whereas W20Y decreased the optimum pH of Xyl1 to 5.0 and slightly increased its specific activity. The N48D mutation also decreased the optimum pH of Xyl1 by one unit. The A134E substitution did not induce any change, but when combined with N48D, a synergistic effect was observed with a 1.4 unit decrease in the optimum pH. Modeling showed that the orientations of residue 193 and of the fully conserved Arg 131 are different in acidophilic and alkaline xylanases whereas the introduced Tyr 20 probably modifies the pKa of the acid-base catalyst via residue Asn 48. Docking of a substrate analog in the catalytic site highlighted striking differences between Xyl1 and XynC in substrate binding. Hydrophobicity calculations showed a correlation between acidophilic adaptation and a decreased hydrophobicity around the two glutamic acid side chains involved in catalysis. [less ▲]

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See detailAn Additional Aromatic Interaction Improves the Thermostability and Thermophilicity of a Mesophilic Family 11 Xylanase: Structural Basis and Molecular Study
Georis, J.; De Lemos Esteves, Frédéric ULg; Lamotte-Brasseur, J. et al

in Protein Science : A Publication of the Protein Society (2000), 9(3), 466-75

In a general approach to the understanding of protein adaptation to high temperature, molecular models of the closely related mesophilic Streptomyces sp. S38 Xyl1 and thermophilic Thermomonospora fusca ... [more ▼]

In a general approach to the understanding of protein adaptation to high temperature, molecular models of the closely related mesophilic Streptomyces sp. S38 Xyl1 and thermophilic Thermomonospora fusca TfxA family 11 xylanases were built and compared with the three-dimensional (3D) structures of homologous enzymes. Some of the structural features identified as potential contributors to the higher thermostability of TfxA were introduced in Xyl1 by site-directed mutagenesis in an attempt to improve its thermostability and thermophilicity. A new Y11-Y16 aromatic interaction, similar to that present in TfxA and created in Xyl1 by the T11Y mutation, improved both the thermophilicity and thermostability. Indeed, the optimum activity temperature (70 vs. 60 degrees C) and the apparent Tm were increased by about 9 degrees C, and the mutant was sixfold more stable at 57 degrees C. The combined mutations A82R/F168H/N169D/delta170 potentially creating a R82-D169 salt bridge homologous to that present in TfxA improved the thermostability but not the thermophilicity. Mutations R82/D170 and S33P seemed to be slightly destabilizing and devoid of influence on the optimal activity temperature of Xyl1. Structural analysis revealed that residues Y11 and Y16 were located on beta-strands B1 and B2, respectively. This interaction should increase the stability of the N-terminal part of Xyl1. Moreover, Y11 and Y16 seem to form an aromatic continuum with five other residues forming putative subsites involved in the binding of xylan (+3, +2, +1, -1, -2). Y11 and Y16 might represent two additional binding subsites (-3, -4) and the T11Y mutation could thus improve substrate binding to the enzyme at higher temperature and thus the thermophilicity of Xyl1. [less ▲]

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