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101.
Breakage of tRNA(Lys(UUU)) by the Escherichia coli anticodon nuclease PrrC (EcoPrrC) underlies a host antiviral response to phage T4 infection that is ultimately thwarted by a virus-encoded RNA repair system. PrrC homologs are prevalent in other bacteria, but their activities and substrates are not defined. We find that induced expression of EcoPrrC is toxic in Saccharomyces cerevisiae and E. coli, whereas the Neisseria meningitidis PrrC (NmePrrC) is not. PrrCs consist of an N-terminal NTPase module and a C-terminal nuclease module. Domain swaps identified the EcoPrrC nuclease domain as decisive for toxicity when linked to either the Eco or Nme NTPase. Indeed, a single arginine-to-tryptophan change in the NmePrrC nuclease domain (R316W) educed a gain-of-function and rendered NmePrrC toxic to yeast, with genetic evidence for tRNA(Lys(UUU)) being the relevant target. The reciprocal Trp-to-Arg change in EcoPrrC (W335R) abolished its toxicity. Further mutagenesis of the EcoPrrC nuclease domain highlighted an ensemble of 15 essential residues and distinguished between hypomorphic alleles and potential nuclease-nulls. We report that the RNA repair phase of the bacterial virus-host dynamic is also portable to yeast, where coexpression of the T4 enzymes Pnkp and Rnl1 ameliorated the toxicity of NmePrrC-R316W. Plant tRNA ligase AtRNL also countered NmePrrC-R316W toxicity, in a manner that depended on AtRNL's 5'-kinase and ligase functions. 相似文献
102.
Meier C Carter LG Sainsbury S Mancini EJ Owens RJ Stuart DI Esnouf RM 《Journal of molecular biology》2008,381(5):1098-1105
Uridine monophosphate (UMP) kinase is a conserved enzyme that catalyzes the ATP-driven conversion of uridylate monophosphate into uridylate diphosphate, an essential metabolic step. In prokaryotes, the enzyme exists as a homohexamer that is regulated by various metabolites. Whereas the enzymatic mechanism of UMP kinase (UK) is well-characterized, the molecular basis of its regulation remains poorly understood. Here we report the crystal structure of UK from Bacillus anthracis (BA1797) in complex with ATP at 2.82 Å resolution. It reveals that the cofactor, in addition to binding in the active sites, also interacts with separate binding pockets located near the center of the hexameric structure. The existence of such an allosteric binding site had been predicted by biochemical studies, but it was not identified in previous crystal structures of prokaryotic UKs. We show that this putative allosteric pocket is conserved across different bacterial species, suggesting that it is a feature common to bacterial UKs, and we present a structural model for the allosteric regulation of this enzyme. 相似文献
103.
104.
Skeletal muscle phosphorylase kinase (PhK) is a Ca2+-dependent enzyme complex, (αβγδ)4, with the δ subunit being tightly bound endogenous calmodulin (CaM). The Ca2+-dependent activation of glycogen phosphorylase by PhK couples muscle contraction with glycogen breakdown in the “excitation-contraction-energy production triad.” Although the Ca2+-dependent protein-protein interactions among the relevant contractile components of muscle are well characterized, such interactions have not been previously examined in the intact PhK complex. Here we show that zero-length cross-linking of the PhK complex produces a covalent dimer of its catalytic γ and CaM subunits. Utilizing mass spectrometry, we determined the residues cross-linked to be in an EF hand of CaM and in a region of the γ subunit sharing high sequence similarity with the Ca2+-sensitive molecular switch of troponin I that is known to bind actin and troponin C, a homolog of CaM. Our findings represent an unusual binding of CaM to a target protein and supply an explanation for the low Ca2+ stoichiometry of PhK that has been reported. They also provide direct structural evidence supporting co-evolution of the coordinate regulation by Ca2+ of contraction and energy production in muscle through the sharing of a common structural motif in troponin I and the catalytic subunit of PhK for their respective interactions with the homologous Ca2+-binding proteins troponin C and CaM. 相似文献
105.
Kazuhisa Sugimoto Koji Nomura Hiromi Nishiura Kohji Ohdan Takahisa Nishimura Hideo Hayashi Takashi Kuriki 《Biologia》2008,63(6):1015-1019
Two sucrose phosphorylases were employed for glycosylation of carboxylic acid compounds. Streptococcus mutans sucrose phosphorylase showed remarkable transglycosylating activity, especially under acidic conditions. Leuconostoc mesenteroides sucrose phosphorylase exhibited very weak transglycosylating activity. Three main products were detected from the reaction
mixture using benzoic acid and sucrose as an acceptor and a donor molecule, respectively. These compounds were identified
as 1-O-benzoyl α-d-glucopyranoside, 2-O-benzoyl α-d-glucopyranose, and 2-O-benzoyl β-d-glucopyranose by 1D-and 2D-NMR analyses of the isolated products and their acetylated products. Time-course analyses proved
that 1-O-benzoyl α-d-glucopyranoside was initially produced by the transglycosylation reaction of the enzyme. 2-O-Benzoyl α-d-glucopyranose and 2-O-benzoyl β-d-glucopyranose were produced from 1-O-benzoyl α-d-glucopyranoside by intramolecular acyl migration reaction. S. mutans sucrose phosphorylase showed broad acceptor-specificity. This sucrose phosphorylase catalyzed transglycosylation to various
carboxylic compounds such as short-chain fatty acids, hydroxy acids, dicarboxylic acids, and phenolic carboxylic acids. 1-O-Acetyl α-d-glucopyranoside was also enzymatically synthesized by transglucosylation reaction of the enzyme. The sensory test of acetic
acid and the glucosides revealed that the sour taste of acetic acid glucosides was significantly lower than that of acetic
acid. 相似文献
106.
Rothermel A Weigel W Pfeiffer-Guglielmi B Hamprecht B Robitzki AA 《Neurochemical research》2008,33(2):336-347
Glycogen is the major energy reserve in neural tissues including the retina. A key-enzyme in glycogen metabolism is glycogen
phosphorylase (GP) which exists in three differentially regulated isoforms. By applying isozyme-specific antibodies it could
be demonstrated that the GP BB (brain), but not the GP MM (muscle) isoform is expressed in the chicken retina in neuronal
and glial (Müller) cells. In the embryonic chicken retina, GP showed a development-dependent expression pattern. Double-labeling
experiments with cell type-specific antibodies revealed that GP is expressed in various layers of the retina some of which,
e.g., the photoreceptor inner segments, are known to be sites of high energy consumption. This suggests important roles of
GP BB, and therefore glycogen, in early differentiation, spontaneous wave generation and in formation and stabilization of
synapses.
Special issue article in honor of Dr. Frode Fonnum. 相似文献
107.
108.
Expression of a bacterial sucrose phosphorylase in potato tubers results in a glucose-independent induction of glycolysis 总被引:7,自引:1,他引:6
R. N. Trethewey A. R. Fernie A. Bachmann H. Fleischer-Notter P. Geigenberger & L. Willmitzer 《Plant, cell & environment》2001,24(3):357-365
Sugars are not only metabolic substrates: they also act as signals that regulate the metabolism of plants. Previously, we found that glycolysis is induced in transgenic tubers expressing a yeast invertase in the cytosol but not in those expressing invertase in the apoplast. This suggests that either the low level of sucrose, the increased formation of cytosolic glucose or the increased levels of metabolites downstream of the sucrose cleavage is responsible for the induction of glycolysis in storage organs. In order to discriminate between these possibilities, we cloned and expressed a bacterial sucrose phosphorylase gene from Pseudomonas saccharophila in potato tubers. Due to the phosphorolytic cleavage of sucrose, formation of glucose was circumvented, thus allowing assessment of the importance of cytosolic glucose – and, by implication, flux through hexokinase – in glycolytic induction. Expression of sucrose phosphorylase led to: (i) a decrease in sucrose content, but no decrease in glucose or fructose; (ii) a decrease in both starch accumulation and tuber yield; (iii) increased levels of glycolytic metabolites; (iv) an induction of the activities of key enzymes of glycolysis; and (v) increased respiratory activity. We conclude that the induction of glycolysis in heterotrophic tissues such as potato tubers occurs via a glucose‐independent mechanism. 相似文献
109.
Reduction of the Edited Domain of the Mitochondrial A6 Gene for ATPase Subunit 6 in Trypanosomatidae
Kolesnikov A. A. Merzlyak E. M. Bessolitsyna E. A. Fedyakov A. V. Shonian G. 《Molecular Biology》2003,37(4):539-543
The sequence of mitochondrial A6 (MURF4) was compared for several trypanosomatids in order to assess the reduction of the edited domain (ED). The association between the ED reduction and the phylogenetic position of a species proved to be less tight than believed earlier. Compared with digenetic species, monogenetic ones more often displayed ED reduction and had smaller ED. 相似文献
110.
Chebotaev D. V. Gul'ko L. B. Veiko V. P. 《Russian Journal of Bioorganic Chemistry》2001,27(3):160-166
Genes for hybrid uridine phosphorylases (UPases) consisting of fragments of amino acid sequences of UPases from Escherichia
coliand Salmonella
typhimuriumwere constructed. Producing strains of the corresponding proteins were genetically engineered. Mutant forms of the E.
coliK-12 UPase were produced by site-directed mutagenesis. A comparative study of the enzyme properties of the mutant and hybrid forms of bacterial UPases was performed. It was shown that Asp27 rather than Asp5 and Asp29 residues of the E
coliUPase forms part of the active site of the protein. A scheme of the involvement of Asp27 in the binding of inorganic phosphate is proposed. 相似文献