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Your search keyword '"Djemel Hamdane"' showing total 3 results
Start Over Author "Djemel Hamdane" Publisher american chemical society (acs)
3 results on '"Djemel Hamdane"'

1. Dihydrouridine in the Transcriptome: New Life for This Ancient RNA Chemical Modification

Author

Damien Brégeon, Ludovic Pecqueur, Sabrine Toubdji, Claudia Sudol, Murielle Lombard, Marc Fontecave, Valérie de Crécy-Lagard, Yuri Motorin, Mark Helm, Djemel Hamdane, hamdane, djemel, Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie des Processus Biologiques (LCPB), Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Collège de France - Chaire Chimie des processus biologiques, Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Florida [Gainesville] (UF), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Ingénierie, Biologie et Santé en Lorraine (IBSLor), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU)

Subjects
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], RNA, Transfer, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Protein Biosynthesis, RNA, Molecular Medicine, RNA, Messenger, General Medicine, RNA Processing, Post-Transcriptional, Transcriptome, Biochemistry
Abstract

International audience; Until recently, post-transcriptional modifications of RNA were largely restricted to noncoding RNA species. However, this belief seems to have quickly dissipated with the growing number of new modifications found in mRNA that were originally thought to be primarily tRNA-specific, such as dihydrouridine. Recently, transcriptomic profiling, metabolic labeling, and proteomics have identified unexpected dihydrouridylation of mRNAs, greatly expanding the catalog of novel mRNA modifications. These data also implicated dihydrouridylation in meiotic chromosome segregation, protein translation rates, and cell proliferation. Dihydrouridylation of tRNAs and mRNAs are introduced by flavin-dependent dihydrouridine synthases. In this review, we will briefly outline the current knowledge on the distribution of dihydrouridines in the transcriptome, their chemical labeling, and highlight structural and mechanistic aspects regarding the dihydrouridine synthases enzyme family. A special emphasis on important research directions to be addressed will also be discussed. This new entry of dihydrouridine into mRNA modifications has definitely added a new layer of information that controls protein synthesis.

Published
2022
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2. Activation of a Unique Flavin-Dependent tRNA-Methylating Agent

Author

Eduardo M. Bruch, Marc Fontecave, Martin J. Field, Sun Un, Djemel Hamdane, RPE Haut Champ des systèmes biologiques ( BHFMR ), Département Biochimie, Biophysique et Biologie Structurale ( B3S ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Institut de biologie structurale ( IBS - UMR 5075 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Laboratoire de Chimie et Biologie des Métaux ( LCBM - UMR 5249 ), RPE Haut Champ des systèmes biologiques (BHFMR), Département Biochimie, Biophysique et Biologie Structurale (B3S), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Chaire Chimie des processus biologiques, Laboratoire de Chimie des Processus Biologiques (LCPB), Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Collège de France - Chaire Chimie des processus biologiques

Subjects
MESH : Models, Chemical, Protein Denaturation, MESH: Hydrogen-Ion Concentration, MESH: Enzyme Stability, MESH: tRNA Methyltransferases, Photochemistry, 01 natural sciences, Biochemistry, chemistry.chemical_compound, RNA, Transfer, Enzyme Stability, MESH : Bacterial Proteins, Methylene, MESH: Bacterial Proteins, Flavin adenine dinucleotide, tRNA Methyltransferases, MESH : Free Radicals, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, MESH: Models, Chemical, MESH : Bacillus subtilis, MESH : Protein Binding, Hydrogen-Ion Concentration, MESH : tRNA Methyltransferases, MESH : Electron Spin Resonance Spectroscopy, MESH: Flavin-Adenine Dinucleotide, MESH : Protein Denaturation, Flavin-Adenine Dinucleotide, Bacillus subtilis, Protein Binding, MESH : Quantum Theory, Free Radicals, Stereochemistry, MESH : RNA, Transfer, Flavin group, 010402 general chemistry, Methylation, Cofactor, Adduct, MESH: Methylation, 03 medical and health sciences, Bacterial Proteins, MESH: Free Radicals, MESH : Hydrogen-Ion Concentration, MESH: Protein Binding, MESH : Flavin-Adenine Dinucleotide, 030304 developmental biology, MESH : Enzyme Stability, TRNA methylation, Electron Spin Resonance Spectroscopy, TRNA Methyltransferase, MESH: Bacillus subtilis, MESH : Methylation, MESH: RNA, Transfer, 0104 chemical sciences, TRNA Methyltransferases, Models, Chemical, chemistry, biology.protein, Quantum Theory, MESH: Electron Spin Resonance Spectroscopy, MESH: Protein Denaturation, MESH: Quantum Theory, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract

International audience; TrmFO is a tRNA methyltransferase that uses methylenetetrahydrofolate (CH2THF) and flavin adenine dinucleotide hydroquinone as cofactors. We have recently shown that TrmFO from Bacillus subtilis stabilizes a TrmFO-CH2-FADH adduct and an ill-defined neutral flavin radical. The adduct contains a unique N-CH2-S moiety, with a methylene group bridging N5 of the isoalloxazine ring and the sulfur of an active-site cysteine (Cys53). In the absence of tRNA substrate, this species is remarkably stable but becomes catalytically competent for tRNA methylation following tRNA addition using the methylene group as the source of methyl. Here, we demonstrate that this dormant methylating agent can be activated at low pH, and we propose that this process is triggered upon tRNA addition. The reaction proceeds via protonation of Cys53, cleavage of the C-S bond, and generation of a highly reactive [FADH(N5)═CH2]+ iminium intermediate, which is proposed to be the actual tRNA-methylating agent. This mechanism is fully supported by DFT calculations. The radical present in TrmFO is characterized here by optical and EPR/ENDOR spectroscopy approaches together with DFT calculations and is shown to be the one-electron oxidized product of the TrmFO-CH2-FADH adduct. It is also relatively stable, and its decomposition is facilitated by high pH. These results provide new insights into the structure and reactivity of the unique flavin-dependent methylating agent used by this class of enzymes.

Published
2013
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3. A Catalytic Intermediate and Several Flavin Redox States Stabilized by Folate-Dependent tRNA Methyltransferase from Bacillus subtilis

Author

Sun Un, Vincent Guérineau, Béatrice Golinelli-Pimpaneau, Djemel Hamdane, Institut de Chimie des Substances Naturelles (ICSN), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)

Subjects
Reducing agent, Stereochemistry, Flavoprotein, Reaction intermediate, Flavin group, 010402 general chemistry, 01 natural sciences, Biochemistry, Catalysis, 03 medical and health sciences, chemistry.chemical_compound, Folic Acid, RNA, Transfer, 030304 developmental biology, Flavin adenine dinucleotide, tRNA Methyltransferases, 0303 health sciences, Binding Sites, TRNA methylation, biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Electron Spin Resonance Spectroscopy, TRNA Methyltransferase, 0104 chemical sciences, TRNA Methyltransferases, Kinetics, Spectrometry, Fluorescence, chemistry, 13. Climate action, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Flavin-Adenine Dinucleotide, biology.protein, Thermodynamics, Oxidation-Reduction, Bacillus subtilis
Abstract

International audience; The flavoprotein TrmFO catalyzes the C5 methylation of uridine 54 in the TΨC loop of tRNAs using 5,10-methylenetetrahydrofolate (CH(2)THF) as a methylene donor and FAD as a reducing agent. Here, we report biochemical and spectroscopic studies that unravel the remarkable capability of Bacillus subtilis TrmFO to stabilize, in the presence of oxygen, several flavin-reduced forms, including an FADH(*) radical, and a catalytic intermediate endowed with methylating activity. The FADH(*) radical was characterized by high-field electron paramagnetic resonance and electron nuclear double-resonance spectroscopies. Interestingly, the enzyme exhibited tRNA methylation activity in the absence of both an added carbon donor and an external reducing agent, indicating that a reaction intermediate, containing presumably CH(2)THF and FAD hydroquinone, is present in the freshly purified enzyme. Isolation by acid treatment, under anaerobic conditions, of noncovalently bound molecules, followed by mass spectrometry analysis, confirmed the presence in TrmFO of nonmodified FAD. Addition of formaldehyde to the purified enzyme protects the reduced flavins from decay by probably preventing degradation of CH(2)THF. The absence of air-stable reduced FAD species during anaerobic titration of oxidized TrmFO, performed in the absence or presence of added CH(2)THF, argues against their thermodynamic stabilization but rather implicates their kinetic trapping by the enzyme. Altogether, the unexpected isolation of a stable catalytic intermediate suggests that the flavin-binding pocket of TrmFO is a highly insulated environment, diverting the reduced FAD present in this intermediate from uncoupled reactions.

Published
2011
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