7-methylguanosine-5--monophosphate has been researched along with 7-methylguanine* in 2 studies
2 other study(ies) available for 7-methylguanosine-5--monophosphate and 7-methylguanine
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Crystal structures of the novel cytosolic 5'-nucleotidase IIIB explain its preference for m7GMP.
5'-nucleotidases catalyze the hydrolytic dephosphorylation of nucleoside monophosphates. As catabolic enzymes they contribute significantly to the regulation of cellular nucleotide levels; misregulation of nucleotide metabolism and nucleotidase deficiencies are associated with a number of diseases. The seven human 5'-nucleotidases differ with respect to substrate specificity and cellular localization. Recently, the novel cytosolic 5'-nucleotidase III-like protein, or cN-IIIB, has been characterized in human and Drosophila. cN-IIIB exhibits a strong substrate preference for the modified nucleotide 7-methylguanosine monophosphate but the structural reason for this preference was unknown. Here, we present crystal structures of cN-IIIB from Drosophila melanogaster bound to the reaction products 7-methylguanosine or cytidine. The structural data reveal that the cytosine- and 7-methylguanine moieties of the products are stacked between two aromatic residues in a coplanar but off-centered position. 7-methylguanosine is specifically bound through π-π interactions and distinguished from unmodified guanosine by additional cation-π coulomb interactions between the aromatic side chains and the positively charged 7-methylguanine. Notably, the base is further stabilized by T-shaped edge-to-face stacking of an additional tryptophan packing perpendicularly against the purine ring and forming, together with the other aromates, an aromatic slot. The structural data in combination with site-directed mutagenesis experiments reveal the molecular basis for the broad substrate specificity of cN-IIIB but also explain the substrate preference for 7-methylguanosine monophosphate. Analyzing the substrate specificities of cN-IIIB and the main pyrimidine 5'-nucleotidase cN-IIIA by mutagenesis studies, we show that cN-IIIA dephosphorylates the purine m7GMP as well, hence redefining its substrate spectrum. Docking calculations with cN-IIIA and m7GMP as well as biochemical data reveal that Asn69 does not generally exclude the turnover of purine substrates thus correcting previous suggestions. Topics: 5'-Nucleotidase; Amino Acid Sequence; Animals; Crystallography, X-Ray; Cytidine; Drosophila melanogaster; Escherichia coli; Gene Expression; Guanine; Humans; Isoenzymes; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Sequence Data; Mutation; Protein Structure, Secondary; Protein Structure, Tertiary; Recombinant Proteins; RNA Cap Analogs; Substrate Specificity; Thermodynamics | 2014 |
Detection of an enzyme activity which cleaves m7 guanine from m7 GMP in an extract of embryonic chick lens cells.
m7Guanine was cleaved from m7GMP by cytoplasmic enzyme activity in an extract prepared from embryonic chick lens cells. The appearance of m7-Guanine was proportional to the time and concentration of extract. m7-Guanine inhibited the reaction but neither guanine nor ribose 5-phosphate did. m7Guanine was not released from m7Guanosine. m7Guanine may be derived from m7GpppG mRNA cap by two enzymatic reactions with m7CMP as a product-substrate intermediate. Topics: Animals; Chick Embryo; Electrophoresis, Paper; Guanine; Kinetics; Lens, Crystalline; RNA Cap Analogs; RNA Caps | 1980 |