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Your search keyword '"MESH: Guanylate Kinase"' showing total 3 results
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3 results on '"MESH: Guanylate Kinase"'

1. Interaction Between CaMKII and GluN2B Controls ERK-Dependent Plasticity

Author

Olivier Moustié, Paul De Koninck, Farida El Gaamouch, Bruno Bontempi, Simon Labrecque, Olivier Nicole, Alain Buisson, Mado Lemieux, Centre-Imagerie, Neurosciences, et Application aux Pathologies (CI-NAPS - UMR 6232), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Equipe 12 : NEuRopathologies et Dysfonctions Synaptiques, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-[GIN] Grenoble Institut des Neurosciences, Institut universitaire en santé mentale de Québec, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from the French Ministry of Research, Alzheimer Foundation, the Agence National de la Recherche (ANR MALZ 2010-001-02 CoRehAlz to B.B.), and Regional Council of Basse-Normandie France (F.E.G., O.N., A.B.), and the Canadian Institutes of Health Research (CIHR) (P.D.K.). M.L. has been supported by studentships from the Natural Science and Engineering Research Council of Canada (NSERC), CIHR, and the Fond de la Recherche en Santé du Québec. S.L. was supported by a CIHR Neurophysics training grant. P.D.K. was a career awardee of CIHR., French Ministry of ResearchAlzheimer FoundationAgence National de la Recherche (ANR MALZ 2010-001-02 CoRehAlz to B.B.)Regional Council of Basse-NormandieCanadian Institutes of Health Research (CIHR)Natural Science and Engineering Research Council of Canada (NSERC),Fond de la Recherche en Santé, NEuRopathologies et Dysfonctions Synaptiques, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre de recherche de l’Institut universitaire en santé mentale de Québec [Canada] (CERVO), Département de réadaptation (Faculté de médecine de l'Université Laval) [Canada], Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval)-Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Faculté de médecine de l'Université Laval [Québec] (ULaval)-Faculté de médecine de l'Université Laval [Québec] (ULaval), and NICOLE, Olivier

Subjects
Cortical neurons, Male, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Neurons, Nonsynaptic plasticity, Mice, 0302 clinical medicine, MESH: Neuronal Plasticity, 4-Aminopyridine, Enzyme Inhibitors, Phosphorylation, RNA, Small Interfering, Neuronal memory allocation, Cells, Cultured, Cerebral Cortex, Neurons, 0303 health sciences, Neuronal Plasticity, Photobleaching, Synaptic scaling, General Neuroscience, Articles, MESH: Calcium-Calmodulin-Dependent Protein Kinase Type 2, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Disks Large Homolog 4 Protein, Microtubule-Associated Proteins, MESH: Photobleaching, MAP Kinase Signaling System, Dendritic Spines, AMPA receptor, In Vitro Techniques, Biology, Bicuculline, Transfection, NMDA receptors, Receptors, N-Methyl-D-Aspartate, Synaptic plasticity, MESH: Dendritic Spines, 03 medical and health sciences, Synaptic augmentation, Metaplasticity, Potassium Channel Blockers, Animals, Immunoprecipitation, GABA-A Receptor Antagonists, MESH: Guanylate Kinase, 030304 developmental biology, Analysis of Variance, MESH: Receptors, N-Methyl-D-Aspartate, MESH: Phosphorylation, MESH: MAP Kinase Signaling System, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Membrane Proteins, MESH: Cerebral Cortex, Rats, Mice, Inbred C57BL, Luminescent Proteins, Synaptic fatigue, Calcium, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Excitatory Amino Acid Antagonists, Guanylate Kinases, Neuroscience, 030217 neurology & neurosurgery
Abstract

International audience; Understanding how brief synaptic events can lead to sustained changes in synaptic structure and strength is a necessary step in solving the rules governing learning and memory. Activation of ERK1/2 (extracellular signal regulated protein kinase 1/2) plays a key role in the control of functional and structural synaptic plasticity. One of the triggering events that activates ERK1/2 cascade is an NMDA receptor (NMDAR)-dependent rise in free intracellular Ca(2+) concentration. However the mechanism by which a short-lasting rise in Ca(2+) concentration is transduced into long-lasting ERK1/2-dependent plasticity remains unknown. Here we demonstrate that although synaptic activation in mouse cultured cortical neurons induces intracellular Ca(2+) elevation via both GluN2A and GluN2B-containing NMDARs, only GluN2B-containing NMDAR activation leads to a long-lasting ERK1/2 phosphorylation. We show that αCaMKII, but not βCaMKII, is critically involved in this GluN2B-dependent activation of ERK1/2 signaling, through a direct interaction between GluN2B and αCaMKII. We then show that interfering with GluN2B/αCaMKII interaction prevents synaptic activity from inducing ERK-dependent increases in synaptic AMPA receptors and spine volume. Thus, in a developing circuit model, the brief activity of synaptic GluN2B-containing receptors and the interaction between GluN2B and αCaMKII have a role in long-term plasticity via the control of ERK1/2 signaling. Our findings suggest that the roles that these major molecular elements have in learning and memory may operate through a common pathway.

Published
2012

2. Complex molecular assemblies at hand via interactive simulations

Author

Olivier Delalande, Nicolas Ferey, G. Grasseau, Marc Baaden, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire de biochimie théorique [Paris] (LBT (UPR_9080)), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), ANR-06-PCVI-0025,FonFlon,Relation fonction/fluctuation structurale chez les protéines(2006), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de biologie physico-chimique (IBPC (FR_550)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), De Villemeur, Hervé, Physique et Chimie du Vivant (PCV) - Relation fonction/fluctuation structurale chez les protéines - - FonFlon2006 - ANR-06-PCVI-0025 - PCVI - VALID, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC (FR_550)), and Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)

Subjects
Models, Molecular, Molecular model, Computer science, MESH: Peptide Hydrolases, Molecular simulation, Chemical, MESH: Escherichia coli Proteins, 010402 general chemistry, 01 natural sciences, Computational science, 03 medical and health sciences, Molecular dynamics, MESH: Software, Interactive simulation, Software, MESH: Computer Simulation, Modelling methods, Models, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Computer Simulation, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Attachment protein, Simulation, MESH: Guanylate Kinase, 030304 developmental biology, 0303 health sciences, business.industry, Escherichia coli Proteins, MESH: Bacterial Outer Membrane Proteins, MESH: Models, Chemical, Molecular, General Chemistry, Guanylate Kinase, 0104 chemical sciences, Computational Mathematics, Models, Chemical, Docking (molecular), business, SNARE Proteins, Guanylate Kinases, MESH: Models, Molecular, Peptide Hydrolases, Bacterial Outer Membrane Proteins, MESH: SNARE Proteins
Abstract

International audience; Studying complex molecular assemblies interactively is becoming an increasingly appealing approach to molecular modeling. Here we focus on interactive molecular dynamics (IMD) as a textbook example for interactive simulation methods. Such simulations can be useful in exploring and generating hypotheses about the structural and mechanical aspects of biomolecular interactions. For the first time, we carry out low-resolution coarse-grain IMD simulations. Such simplified modeling methods currently appear to be more suitable for interactive experiments and represent a well-balanced compromise between an important gain in computational speed versus a moderate loss in modeling accuracy compared to higher resolution all-atom simulations. This is particularly useful for initial exploration and hypothesis development for rare molecular interaction events. We evaluate which applications are currently feasible using molecular assemblies from 1900 to over 300,000 particles. Three biochemical systems are discussed: the guanylate kinase (GK) enzyme, the outer membrane protease T and the soluble N-ethylmaleimide-sensitive factor attachment protein receptors complex involved in membrane fusion. We induce large conformational changes, carry out interactive docking experiments, probe lipid-protein interactions and are able to sense the mechanical properties of a molecular model. Furthermore, such interactive simulations facilitate exploration of modeling parameters for method improvement. For the purpose of these simulations, we have developed a freely available software library called MDDriver. It uses the IMD protocol from NAMD and facilitates the implementation and application of interactive simulations. With MDDriver it becomes very easy to render any particle-based molecular simulation engine interactive. Here we use its implementation in the Gromacs software as an example.

Published
2009

3. Unique GMP-binding site in Mycobacterium tuberculosis guanosine monophosphate kinase

Author

Edward Seclaman, Eric Girard, Louis Renault, Petya Christova, Jacqueline Cherfils, G. Hible, Hélène Munier-Lehmann, Andrew Thompson, Laboratoire d'enzymologie et biochimie structurales (LEBS), Centre National de la Recherche Scientifique (CNRS), Institute of Organic Chemistry, Bulgarian Academy of Sciences (BAS), Chimie Organique, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Synchrotron SOLEIL (SSOLEIL), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Mycobacterium tuberculosis, Guanylate kinase, Guanosine Monophosphate, MESH: Guanosine Diphosphate, Biology, Crystallography, X-Ray, Guanosine Diphosphate, Biochemistry, Catalysis, Serine, MESH: Recombinant Proteins, 03 medical and health sciences, MESH: 5'-Guanylic Acid, Bacterial Proteins, Structural Biology, Transferase, MESH: Cloning, Molecular, Cloning, Molecular, Structural motif, Molecular Biology, MESH: Bacterial Proteins, MESH: Guanylate Kinase, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Binding Sites, MESH: Kinetics, Kinase, GMP binding, 030302 biochemistry & molecular biology, Mycobacterium tuberculosis, MESH: Catalysis, MESH: Crystallography, X-Ray, Recombinant Proteins, 3. Good health, Kinetics, Enzyme, chemistry, MESH: Binding Sites, Guanylate Kinases, Nucleoside
Abstract

Bacterial nucleoside monophos- phate (NMP) kinases, which convert NMPs to nucleo- side diphosphates (NDP), are investigated as poten- tial antibacterial targets against pathogenic bacteria. Herein, we report the biochemical and structural characterization of GMP kinase from Mycobacterium tuberculosis (GMPKMt). GMPKMt is a monomer with an unusual specificity for ATP as a phosphate donor, a lower catalytic efficiency com- pared with eukaryotic GMPKs, and it carries two redox-sensitive cysteines in the central CORE do- main. These properties were analyzed in the light of the high-resolution crystal structures of unbound, GMP-bound, and GDP-bound GMPKMt. The latter structure was obtained in both an oxidized form, in which the cysteines form a disulfide bridge, and a reduced form which is expected to correspond to the physiological enzyme. GMPKMt has a modular domain structure as most NMP kinases. However, it departs from eukaryotic GMPKs by the unusual conformation of its CORE domain, and by its par- tially open LID and GMP-binding domains which are the same in the apo-, GMP-bound, and GDP- bound forms. GMPKMt also features a unique GMP binding site which is less close-packed than that of mammalian GMPKs, and in which the replacement of a critical tyrosine by a serine removes a catalytic interaction. In contrast, the specificity of GMPKMt for ATP may be a general feature of GMPKs because of an invariant structural motif that recognizes the adenine base. Altogether, differences in domain dynamics and GMP binding between GMPKMt and mammalian GMPKs should reveal clues for the de- sign of GMPKMt-specific inhibitors. Proteins 2006; 62:489 -500. © 2005 Wiley-Liss, Inc.

Published
2006

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