The Experts below are selected from a list of 10710 Experts worldwide ranked by ideXlab platform
Michel Veron - One of the best experts on this subject based on the ideXlab platform.
-
ACTIVATION OF ANTI-REVERSE TRANSCRIPTASE NUCLEOTIDE ANALOGS BY NUCLEOSIDE DIPHOSPHATE Kinase: IMPROVEMENT BY α-BORANOPHOSPHATE SUBSTITUTION
Nucleosides nucleotides & nucleic acids, 2001Co-Authors: Benoit Schneider, Joël Janin, Michel Veron, Philippe Meyer, Simon Sarfati, Laurence A. Mulard, Catherine Guerreiro, Joëlle Boretto, Dominique Deville-bonne, Bruno CanardAbstract:Nucleoside activation by nucleoside diphosphate Kinase and inhibition of HIV-1 reverse transcriptase were studied comparatively for a new class of nucleoside analogs with a borano (BH− 3) or a thio (SH) group on the α-phosphate. Both the α-Rp-borano derivatives of AZT and d4T improved phosphorylation by NDP Kinase, inhibition of reverse transcription as well as stability of α-borano monophosphate derivatives in terminated viral DNA chain.
-
Coupling between Catalysis and Oligomeric Structure in Nucleoside Diphosphate Kinase
The Journal of biological chemistry, 1998Co-Authors: Sébastien Mesnildrey, Fabrice Agou, Anna Karlsson, Dominique Deville Bonne, Michel VeronAbstract:Abstract A dimeric Dictyostelium nucleoside diphosphate Kinase has been stabilized by the double mutation P100S-N150stop which targets residues involved in the trimer interface (Karlsson, A., Mesnildrey, S., Xu, Y., Morera, S., Janin, J., and Veron, M. (1996) J. Biol. Chem. 271, 19928–19934). The reassociation of this dimeric form into a hexamer similar to the wild-type enzyme is induced by the presence of a nucleotide substrate. Equilibrium sedimentation and gel filtration experiments, as well as enzymatic activity measurements, show that reactivation of the enzyme closely parallels its reassociation. A phosphorylatable intermediate with low activity participates in the association pathway while the dimeric form is shown totally devoid of enzymatic activity. Our results support the hypothesis that different oligomeric species of nucleoside diphosphate Kinase are involved in different cellular processes where the enzymatic activity is not required.
-
Nucleoside Diphosphate Kinase: Effect of the P100S Mutation on Activity and Quaternary Structure
Interacting Protein Domains, 1997Co-Authors: Sébastien Mesnildrey, Michel VeronAbstract:Nucleoside Diphosphate Kinase (NDP Kinase) is an ubiquitous enzyme which catalyses the phosphate exchange between a triphospho-and a diphospho-nucleoside by a ping-pong mechanism involving the formation of a phospho-histidine intermediate [1,2]. The enzyme is not specific and can use both ribo- and deoxyribonucleotides as well as purines and pyrimidines as subtrates.
-
Investigation of the active site and the conformational stability of nucleoside diphosphate Kinase by site-directed mutagenesis.
The Journal of biological chemistry, 1994Co-Authors: Annemiek D. Tepper, H Dammann, A A Bominaar, Michel VeronAbstract:Abstract Nucleoside-Diphosphate Kinase (EC 2.7.4.6) catalyzes phosphate exchange between nucleoside triphosphates and nucleoside diphosphates. Its 17 kDa subunits are highly conserved throughout evolution in both sequence and tertiary structure. Using site-directed mutagenesis we investigated the function of 8 amino acids (Lys16, Tyr56, Arg92, Thr98, Arg109, Asn119, Ser124, and Glu133) that are totally conserved among all nucleoside diphosphate Kinases known to date. The mutant proteins all show decreased specific activity and support roles for these residues in catalysis, substrate binding, or both, as was previously proposed on the basis of the x-ray structure (Morera, S., Lascu, I., Dumas, C., LeBras, G., Briozzo, P., Veron, M., and Janin, J. (1994) Biochemistry 33, 459-467). Furthermore, residues Lys16, Arg109, and Asn 119 were identified to play important roles in conformational stability or subunit interactions. We show that Lys16 and Asn119 form a rigid structure that is important for enzymatic function and that Arg109, known to interact with the phosphate moiety of the substrate, also plays an important role in subunit association. The dual roles of Lys16, Arg109, and Asn119 in both substrate binding and subunit assembly provide further evidence for a functional coupling between catalytic activity and quaternary structure in nucleoside diphosphate Kinase.
-
Assay of nucleoside diphosphate Kinase in microtiter plates using a peroxidase-coupled method
Analytical biochemistry, 1993Co-Authors: Ioan Lascu, Marie-lise Lacombe, K. Leblay, E. Presecan, Michel VeronAbstract:A sensitive assay for nucleoside diphosphate Kinase which utilizes microtiter plates is described. ATP, formed in the reaction between dGTP and ADP, is trapped by the glycerol Kinase reaction. A colored compound is generated by glycerol-3-phosphate oxidase and peroxidase. This assay is useful for testing a large number of samples generated by chromatographic techniques or for screening purposes.
Carina Knorpp - One of the best experts on this subject based on the ideXlab platform.
-
Structure and Mutational Analysis of a Plant Mitochondrial Nucleoside Diphosphate Kinase. Identification of Residues Involved in Serine Phosphorylation and Oligomerization
Plant physiology, 2004Co-Authors: Monika Johansson, Alasdair Mackenzie-hose, Inger Andersson, Carina KnorppAbstract:We report the first crystal structure of a plant (Pisum sativum L. cv Oregon sugarpod) mitochondrial nucleoside diphosphate Kinase. Similar to other eukaryotic nucleoside diphosphate Kinases, the plant enzyme is a hexamer; the six monomers in the asymmetric unit are arranged as trimers of dimers. Different functions of the Kinase have been correlated with the oligomeric structure and the phosphorylation of Ser residues. We show that the occurrence of Ser autophosphorylation depends on enzymatic activity. The mutation of the strictly conserved Ser-119 to Ala reduced the Ser phosphorylation to about one-half of that observed in wild type with only a modest change of enzyme activity. We also show that mutating another strictly conserved Ser, Ser-69, to Ala reduces the enzyme activity to 6% and 14% of wild-type using dCDP and dTDP as acceptors, respectively. Changes in the oligomerization pattern of the S69A mutant were observed by cross-linking experiments. A reduction in trimer formation and a change in the dimer interaction could be detected with a concomitant increase of tetramers. We conclude that the S69 mutant is involved in the stabilization of the oligomeric state of this plant nucleoside diphosphate Kinase.
-
Plant mitochondrial nucleoside diphosphate Kinase is attached to the membrane through interaction with the adenine nucleotide translocator.
FEBS letters, 2003Co-Authors: Carina Knorpp, Monika Johansson, Anne-marie BairdAbstract:This study shows that the plant mitochondrial nucleoside diphosphate Kinase (mNDPK) localizes to both the intermembrane space and to the mitochondrial inner membrane. We show that mNDPK is very firmly attached to the membrane. Co-immunoprecipitation experiments identified the adenine nucleotide translocator as an interaction partner. This is the first report showing a direct association between these two proteins, although previous studies have shown metabolic cooperation between them. Possible consequences for mitochondrial energy metabolism are discussed.
Marie-lise Lacombe - One of the best experts on this subject based on the ideXlab platform.
-
The mitochondrial nucleoside diphosphate Kinase (NDPK-D/NME4), a moonlighting protein for cell homeostasis.
Laboratory investigation; a journal of technical methods and pathology, 2018Co-Authors: Marie-lise Lacombe, Malgorzata Tokarska-schlattner, Mathieu Boissan, Uwe SchlattnerAbstract:Mitochondrial nucleoside diphosphate Kinase (NDPK-D; synonyms: NME4, NM23-H4) represents the major mitochondrial NDP Kinase. The homohexameric complex emerged as a protein with multiple functions in bioenergetics and phospholipid signaling. It occurs at different but precise mitochondrial locations and can affect among other mitochondrial shapes and dynamics, as well as the specific elimination of defective mitochondria or cells via mitophagy or apoptosis. With these various functions in cell homeostasis, NDPK-D/NME4 adds to the group of so-called moonlighting (or gene sharing) proteins.
-
NME4/nucleoside diphosphate Kinase D in cardiolipin signaling and mitophagy
Laboratory Investigation, 2018Co-Authors: Uwe Schlattner, Marie-lise Lacombe, Malgorzata Tokarska-schlattner, Mathieu Boissan, Richard Epand, Valerian KaganAbstract:Mitophagy is an emerging paradigm for mitochondrial quality control and cell homeostasis. Dysregulation of mitophagy can lead to human pathologies such as neurodegenerative disorders and contributes to the aging process. Complex protein signaling cascades have been described that regulate mitophagy. We have identified a novel lipid signaling pathway that involves the phospholipid cardiolipin (CL). CL is synthesized and normally confined at the inner mitochondrial membrane. However, upon a mitophagic trigger, ie, collapse of the inner membrane potential, CL is rapidly externalized to the mitochondrial surface with the assistance of the hexameric nucleoside diphosphate Kinase D (NME4, NDPK-D, or NM23-H4). In addition to its NDP Kinase activity, NME4/NDPK-D shows intermembrane phospholipid transfer activity in vitro and in cellular systems, which relies on NME4/NDPK-D interaction with CL, CL-dependent crosslinking of inner and outer mitochondrial membranes by symmetrical, hexameric NME4/NDPK-D, and a putative NME4/NDPK-D-based CL-transfer pathway. CL exposed at the mitochondrial surface then serves as an 'eat me' signal for the mitophagic machinery; it is recognized by the LC3 receptor of autophagosomes, targeting the dysfunctional mitochondrion to lysosomal degradation. Similar NME4-supported CL externalization is likely also involved in apoptosis and inflammatory reactions.
-
A point mutation of human nucleoside diphosphate Kinase A found in aggressive neuroblastoma affects protein folding.
The Journal of biological chemistry, 1997Co-Authors: Ioan Lascu, Marie-lise Lacombe, Sabine Schaertl, Chanquing Wang, Claude Sarger, Anna Giartosio, Gilberd Briand, Manfred KonradAbstract:Abstract The point mutation serine 120 to glycine in the human nucleoside diphosphate Kinase A has been identified in several aggressive neuroblastomas (Chang, C. L., Zhu, X. X., Thoraval, D. H., Ungar, D., Rawwas, J., Hora, N., Strahler, J. R., Hanash, S. M. & Radany, E. (1994) Nature 370, 335–336). We expressed in bacteria and purified wild-type and S120G mutant nucleoside diphosphate Kinase A. The mutant enzyme had enzymatic and structural properties similar to the wild-type enzyme, whereas its stability to denaturation by heat and urea was markedly reduced. More importantly, upon renaturation of the urea-denatured mutant protein, a folding intermediate accumulated, having the characteristics of a molten globule. It had no tertiary structure, as shown by near UV circular dichroism, whereas the secondary structure was substantially recovered. The hydrophobic probe 8-anilino-1-naphthalene sulfonate bound to the intermediate species with an increase in fluorescence intensity and a blue shift. The hydrodynamic size was between that expected for a folded and an unfolded monomer. Finally, electrophoresis in a transverse urea gradient displayed no renaturation curve, and the protein showed the tendency to aggregate at the lowest urea concentrations. The existence of a molten globule folding intermediates resulting from an altered folding in the mutated protein might be related to the aggressiveness of neuroblastomas.
-
Assay of nucleoside diphosphate Kinase in microtiter plates using a peroxidase-coupled method
Analytical biochemistry, 1993Co-Authors: Ioan Lascu, Marie-lise Lacombe, K. Leblay, E. Presecan, Michel VeronAbstract:A sensitive assay for nucleoside diphosphate Kinase which utilizes microtiter plates is described. ATP, formed in the reaction between dGTP and ADP, is trapped by the glycerol Kinase reaction. A colored compound is generated by glycerol-3-phosphate oxidase and peroxidase. This assay is useful for testing a large number of samples generated by chromatographic techniques or for screening purposes.
-
X-ray structure of nucleoside diphosphate Kinase.
The EMBO journal, 1992Co-Authors: Christian Dumas, Valérie Wallet, Marie-lise Lacombe, Michel Veron, Solange Moréra, Ioan Lascu, Philippe Glaser, R. Fourme, Joël JaninAbstract:The X-ray structure of a point mutant of nucleoside diphosphate Kinase (NDP Kinase) from Dictyostelium discoideum has been determined to 2.2 A resolution. The enzyme is a hexamer made of identical subunits with a novel mononucleotide binding fold. Each subunit contains an alpha/beta domain with a four stranded, antiparallel beta-sheet. The topology is different from adenylate Kinase, but identical to the allosteric domain of Escherichia coli ATCase regulatory subunits, which bind mononucleotides at an equivalent position. Dimer contacts between NDP Kinase subunits within the hexamer are similar to those in ATCase. Trimer contacts involve a large loop of polypeptide chain that bears the site of the Pro----Ser substitution in Killer of prune (K-pn) mutants of the highly homologous Drosophila enzyme. Properties of Drosophila NDP Kinase, the product of the awd developmental gene, and of the human enzyme, the product of the nm23 genes in tumorigenesis, are discussed in view of the three-dimensional structure and of possible interactions of NDP Kinase with other nucleotide binding proteins.
Monika Johansson - One of the best experts on this subject based on the ideXlab platform.
-
Structure and Mutational Analysis of a Plant Mitochondrial Nucleoside Diphosphate Kinase. Identification of Residues Involved in Serine Phosphorylation and Oligomerization
Plant physiology, 2004Co-Authors: Monika Johansson, Alasdair Mackenzie-hose, Inger Andersson, Carina KnorppAbstract:We report the first crystal structure of a plant (Pisum sativum L. cv Oregon sugarpod) mitochondrial nucleoside diphosphate Kinase. Similar to other eukaryotic nucleoside diphosphate Kinases, the plant enzyme is a hexamer; the six monomers in the asymmetric unit are arranged as trimers of dimers. Different functions of the Kinase have been correlated with the oligomeric structure and the phosphorylation of Ser residues. We show that the occurrence of Ser autophosphorylation depends on enzymatic activity. The mutation of the strictly conserved Ser-119 to Ala reduced the Ser phosphorylation to about one-half of that observed in wild type with only a modest change of enzyme activity. We also show that mutating another strictly conserved Ser, Ser-69, to Ala reduces the enzyme activity to 6% and 14% of wild-type using dCDP and dTDP as acceptors, respectively. Changes in the oligomerization pattern of the S69A mutant were observed by cross-linking experiments. A reduction in trimer formation and a change in the dimer interaction could be detected with a concomitant increase of tetramers. We conclude that the S69 mutant is involved in the stabilization of the oligomeric state of this plant nucleoside diphosphate Kinase.
-
Plant mitochondrial nucleoside diphosphate Kinase is attached to the membrane through interaction with the adenine nucleotide translocator.
FEBS letters, 2003Co-Authors: Carina Knorpp, Monika Johansson, Anne-marie BairdAbstract:This study shows that the plant mitochondrial nucleoside diphosphate Kinase (mNDPK) localizes to both the intermembrane space and to the mitochondrial inner membrane. We show that mNDPK is very firmly attached to the membrane. Co-immunoprecipitation experiments identified the adenine nucleotide translocator as an interaction partner. This is the first report showing a direct association between these two proteins, although previous studies have shown metabolic cooperation between them. Possible consequences for mitochondrial energy metabolism are discussed.
David O. Lambeth - One of the best experts on this subject based on the ideXlab platform.
-
The compartmentation of nucleoside diphosphate Kinase in mitochondria.
Comparative biochemistry and physiology. Part B Biochemistry & molecular biology, 1995Co-Authors: Wallace W. Muhonen, David O. LambethAbstract:The compartmentation of nucleoside diphosphate Kinase (NDPK) was studied in mitochondria isolated from heart and liver of rat, rabbit, and pigeon. Compartmentation was assessed by determining latencies of enzyme activities, fractionating mitochondria with digitonin, and treating mitochondria with trypsin in the presence and absence of digitonin. NDPK activity in pigeon liver mitochondria was five- and seven-fold higher than in rat and rabbit liver mitochondria. The ratios of NDPK activities in liver vs. heart mitochondria were about 15 for rat, 2 for rabbit, and more than 40 for pigeon. Nearly all NDPK in pigeon liver mitochondria is in the matrix space, but outside the matrix in rat and rabbit liver mitochondria. Most NDPK in pigeon heart mitochondria was located outside the matrix while a significant fraction may be in the matrix of rat and rabbit heart mitochondria. These results are discussed relative to the assumed role that mitochondrial NDPK transfers the phosphoryl group of GTP produced in the Krebs cycle to the adenine nucleotide pool.
-
Apparent ATP-linked succinate thioKinase activity and its relation to nucleoside diphosphate Kinase in mitochondrial matrix preparations from rabbit.
Biochimica et biophysica acta, 1991Co-Authors: Eddie F. Kadrmas, Paul D. Ray, David O. LambethAbstract:Abstract The relative abilities of ATP and GTP to support succinyl-CoA synthesis by mitochondrial matrix fractions prepared from rabbit heart and liver mitoplasts were investigated. The activity supported by ATP in rabbit heart preparations was less than 15% of that obtained with GTP, while no ATP-supported activity was observed in rabbit liver preparations. However, the addition of 30 micromolar GDP to matrix fractions from either heart or liver stimulated the ATP-supported activity to 40% of that observed with GTP, and the further addition of bovine liver nucleoside diphosphate Kinase in the presence of 8 μM added GDP increased the activity to near that observed with GTP. The specific activity of nucleoside diphosphate Kinase assayed directly in mitochondrial matrix from heart was about 15% of the specific activity of ATP-supported succinate thioKinase induced upon adding GDP. Evidence for a complex between nucleoside diphosphate Kinase and succinate thioKinase in mitochondrial matrix from rabbit heart was obtained by glycerol density gradient centrifugation. It is proposed that binding of nucleoside diphosphate Kinase to succinate thioKinase activates the former enzyme, accounts for the ATP-supported succinyl-CoA synthetase activity observed, and is involved in the channeling of high energy phosphate from GTP produced in the Krebs cycle to the ATP pool.
