5bv3 | pdb_00005bv3
Yeast Scavenger Decapping Enzyme in complex with m7GDP
Structural highlights
FunctionDCPS_YEAST Decapping scavenger enzyme that catalyzes the cleavage of a residual cap structure following the degradation of mRNAs by the 3'->5' exosome-mediated mRNA decay pathway. Hydrolyzes cap analog structures like 7-methylguanosine nucleoside triphosphate (m7GpppG) and tri-methyl guanosine nucleoside triphosphate (m3(2,2,7)GpppG) with up to 10 nucleotide substrates (small capped oligoribonucleotides) and specifically releases 5'-phosphorylated RNA fragments and 7-methylguanosine monophosphate (m7GMP) or tri-methyl guanosine nucleoside monophosphate (m3(2,2,7)GMP), respectively. Does not hydrolyze unmethylated cap analog (GpppG) and shows no decapping activity on intact m7GpppG-capped mRNA molecules longer than 25 nucleotides. Does not hydrolyze 7-methylguanosine diphosphate (m7GDP) and tri-methylguanosine diphosphate (m3(2,2,7)GDP) to (m(7)GMP) and m3(2,2,7)GMP, respectively (PubMed:22985415). May also play a role in the 5'->3 mRNA decay pathway; m7GDP, the downstream product released by the 5'->3' mRNA mediated decapping activity, may be also converted by DCS1 to m7GMP (PubMed:14523240). Binds to m7GpppG and strongly to m7GDP. May also regulates the 5'->3' exoribonucleolytic mRNA decay pathway in a cap-independent manner. Negatively regulates trehalase activity.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedThe scavenger decapping enzyme hydrolyzes the protective 5' cap structure on short mRNA fragments that are generated from the exosomal degradation of mRNAs. From static crystal structures and NMR data, it is apparent that the dimeric enzyme has to undergo large structural changes to bind its substrate in a catalytically competent conformation. Here we studied the yeast enzyme and showed that the associated opening and closing motions can be orders of magnitude faster than the catalytic turnover rate. This excess of motion is induced by the binding of a second ligand to the enzyme, which occurs at high substrate concentrations. We designed a mutant that disrupted the allosteric pathway that links the second binding event to the dynamics and showed that this mutant enzyme is hyperactive. Our data reveal a unique mechanism of substrate inhibition in which motions that are required for catalytic activity also inhibit efficient turnover when they are present in excess. An excess of catalytically required motions inhibits the scavenger decapping enzyme.,Neu A, Neu U, Fuchs AL, Schlager B, Sprangers R Nat Chem Biol. 2015 Sep;11(9):697-704. doi: 10.1038/nchembio.1866. Epub 2015 Aug , 10. PMID:26258763[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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