C[n+]1cn([C@@H]2O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])(=O)O-*)[C@@H](O)[C@H]2O)c2nc(N)[nH]c(=O)c12 |
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Outgoing
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7-methylguanosine 5'-triphosphate(2−) group
(CHEBI:74429)
is a
organic anionic group
(CHEBI:64775)
7-methylguanosine 5'-triphosphate(2−) group
(CHEBI:74429)
is conjugate base of
7-methylguanosine 5'-triphosphate group
(CHEBI:74655)
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Incoming
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5'-(N7-methyl 5'-triphosphoguanosine)-(2'-O-methyl-purine-ribonucleotide)(2−) residue
(CHEBI:133969)
has functional parent
7-methylguanosine 5'-triphosphate(2−) group
(CHEBI:74429)
5'-(N7-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleoside)(2−) residue
(CHEBI:167609)
has functional parent
7-methylguanosine 5'-triphosphate(2−) group
(CHEBI:74429)
5'-(N7-methyl 5'-triphosphoguanosine)-(purine-ribonucleotide)(2−) residue
(CHEBI:133968)
has functional parent
7-methylguanosine 5'-triphosphate(2−) group
(CHEBI:74429)
7-methylguanosine 5'-triphosphate group
(CHEBI:74655)
is conjugate acid of
7-methylguanosine 5'-triphosphate(2−) group
(CHEBI:74429)
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5'-(N7-methyl 5'-triphosphoguanosine) group
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SUBMITTER
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m7GpppX
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SUBMITTER
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N7-methylguanosine 5'-triphosphate group
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UniProt
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Liu SW, Rajagopal V, Patel SS, Kiledjian M (2008) Mechanistic and kinetic analysis of the DcpS scavenger decapping enzyme. The Journal of biological chemistry 283, 16427-16436 (Source: SUBMITTER) [PubMed:18441014] [show Abstract] Decapping is an important process in the control of eukaryotic mRNA degradation. The scavenger decapping enzyme DcpS functions to clear the cell of cap structure following decay of the RNA body by catalyzing the hydrolysis of m(7)GpppN to m(7)Gp and ppN. Structural analysis has revealed that DcpS is a dimeric protein with a domain-swapped amino terminus. The protein dimer contains two cap binding/hydrolysis sites and displays a symmetric structure with both binding sites in the open conformation in the ligand-free state and an asymmetric conformation with one site open and one site closed in the ligand-bound state. The structural data are suggestive of a dynamic decapping mechanism where each monomer could alternate between an open and closed state. Using transient state kinetic studies, we show that both the rate-limiting step and rate of decapping are regulated by cap substrate. A regulatory mechanism is established by the intrinsic domain-swapped structure of the DcpS dimer such that the decapping reaction is very efficient at low cap substrate concentrations yet regulated with excess cap substrate. These data provide biochemical evidence to verify experimentally a dynamic and mutually exclusive cap hydrolysis activity of the two cap binding sites of DcpS and provide key insights into its regulation. | Malys N, McCarthy JE (2006) Dcs2, a novel stress-induced modulator of m7GpppX pyrophosphatase activity that locates to P bodies. Journal of molecular biology 363, 370-382 (Source: SUBMITTER) [PubMed:16963086] [show Abstract] The eukaryotic "scavenger" type decapping enzyme, an m(7)GpppX pyrophosphatase, is active in cellular mRNA metabolism and thereby influences posttranscriptional gene expression. The yeast version of this enzyme, Dcs1, catalyses cleavage of 5'end m(7)G-oligoribonucleotide fragments generated by 3'-->5' exonucleolytic decay, and cleavage of m(7)GDP generated by Dcp1/Dcp2-mediated decapping in the 5'-->3' decay pathway. We show that Dcs1 is active as a homodimer with low KM values for cleavage of m(7)GpppG (0.14 microM) and m(7)GDP (0.26 microM). Previous work showed that the paralogous DCS2 gene is transcriptionally induced via the amp-PKA pathway as yeast enters diauxie. The resulting Dcs2 protein forms a heterodimer together with Dcs1, both modulating Dcs1 substrate specificity and suppressing its k(cat). Since Dcs2 is recruited into cytoplasmic P bodies, its inhibitory function may be focused in these centres of mRNA storage/turnover. Dcs2 is therefore a novel type of stress-induced regulatory protein that modulates m(7)GpppX pyrophosphatase activity. Moreover, inhibition of Dcs1 activity by Dcs2, like depletion of Dcs1, reduces chronological life span, possibly by modulating m(7)G misincorporation into nucleic acids. This could potentially link control of mRNA metabolism with senescence. | Chen N, Walsh MA, Liu Y, Parker R, Song H (2005) Crystal structures of human DcpS in ligand-free and m7GDP-bound forms suggest a dynamic mechanism for scavenger mRNA decapping. Journal of molecular biology 347, 707-718 (Source: SUBMITTER) [PubMed:15769464] [show Abstract] Eukaryotic cells utilize DcpS, a scavenger decapping enzyme, to degrade the residual cap structure following 3'-5' mRNA decay, thereby preventing the premature decapping of the capped long mRNA and misincorporation of methylated nucleotides in nucleic acids. We report the structures of DcpS in ligand-free form and in a complex with m7GDP. apo-DcpS is a symmetric dimer, strikingly different from the asymmetric dimer observed in the structures of DcpS with bound cap analogues. In contrast, and similar to the m7GpppG-DcpS complex, DcpS with bound m7GDP is an asymmetric dimer in which the closed state appears to be the substrate-bound complex, whereas the open state mimics the product-bound complex. Comparisons of these structures revealed conformational changes of both the N-terminal swapped-dimeric domain and the cap-binding pocket upon cap binding. Moreover, Tyr273 in the cap-binding pocket displays remarkable conformational changes upon cap binding. Mutagenesis and biochemical analysis suggest that Tyr273 seems to play an important role in cap binding and product release. Examination of the crystallographic B-factors indicates that the N-terminal domain in apo-DcpS is inherently flexible, and in a dynamic state ready for substrate binding and product release. |
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