Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 5'-cap structure of eukaryotic mRNA is methylated at the terminal guanosine by RNA (guanine-N7-)-methyltransferase (cap MTase). Saccharomyces cerevisiae ABD1 (ScABD1) and human hMet (also called CMT1) genes are responsible for this enzyme. The ABD1 homologue was cloned from the pathogenic fungus Candida albicans and named C. albicans ABD1 (CaABD1). When expressed as a fusion with glutathione S-transferase (GST), CaAbd1p displayed cap MTase activity in vitro and rescued S. cerevisiae abd1delta null mutants, indicating that CaABD1 specifies an active cap MTase. Although the human cap MTase binds to the human capping enzyme (Hce1p), which possesses both mRNA guanylyltransferase (mRNA GTase) and mRNA 5'-triphosphatase (mRNA TPase) activities, yeast two-hybrid analysis demonstrated that in yeast neither mRNA GTase nor mRNA TPase physically interacted with the Abd1 protein. Comparison of the amino acid sequences of known and putative cap MTases revealed a highly conserved amino acid sequence motif, Phe/Val-Leu-Asp/Glu-Leu/Met-Xaa-Cys-Gly-Lys-Gly-Gly-Asp-Leu-Xaa-Lys, which encompasses the sequence motif characteristic of divergent methyltransferases. Mutations in CaAbd1p of leucine at the second and the twelfth positions (so far uncharacterized) to alanine severely diminished the enzyme activity and the functionality in vivo, whereas those of leucine at the fourth, cysteine at the sixth, lysine at the eighth, and glycine at the tenth positions did not. Furthermore, valine substitution for the twelfth, but not for the second, leucine in that motif abolished the activity and functionality of CaAbd1p. Thus, it appears that leucine at the second and the twelfth positions in the motif, together with a previously identified acidic residue in the third, glycine at the sixth and glutamic acid at the eleventh positions, play important roles in the catalysis, and that side chain length is crucial for the activity at the twelfth position in the motif.
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PMID:The Candida albicans gene for mRNA 5-cap methyltransferase: identification of additional residues essential for catalysis. 1058 10

We screened a human cDNA library for proteins that bind mRNA cap methyltransferase (MT) and isolated nuclear transporter importin-alpha (Impalpha). This direct association was confirmed by glutathione S-transferase (GST) pulldown, coimmunoprecipitation, and nuclear colocalization. In gel shift assays, MT selectively bound RNA containing 5'-terminal GpppG, and binding was inhibited by GpppG and not by m(7)GpppC. Impalpha markedly enhanced MT binding to GpppG-RNA and stimulated MT activity. MT/RNA/Impalpha complexes were dissociated by importin-beta, which also blocked the stimulation of cap methylation by Impalpha. The presence of RanGTP but not RanGDP prevented these effects of importin-beta. These findings indicate that importins play a novel role in mRNA biogenesis at the level of cap methylation.
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PMID:Cap methyltransferase selective binding and methylation of GpppG-RNA are stimulated by importin-alpha. 1111 84