Abstract of the PDB Structure's related Publication:
Complete removal of residual N-7 guanine cap from degraded messenger RNA is necessary to prevent accumulation of intermediates that might interfere with RNA processing, export, and translation. The human scavenger decapping enzyme, DcpS, catalyzes residual cap hydrolysis following mRNA degradation, releasing N-7 methyl guanosine monophosphate and 5'-diphosphate terminated cap or mRNA products. DcpS structures bound to m(7)GpppG or m(7)GpppA reveal an asymmetric DcpS dimer that simultaneously creates an open nonproductive DcpS-cap complex and a closed productive DcpS-cap complex that alternate via 30 A domain movements. Structural and biochemical analysis suggests an autoregulatory mechanism whereby premature decapping mRNA is prevented by blocking the conformational changes that are required to form a closed productive active site capable of cap hydrolysis.
DCPS is a decapping scavenger enzyme that hydrolyzes residual cap structure following the 3’-to-5’ exosome-mediated mRNA decay pathway. Moreover, it catalyzes the cleavage of cap analog structures like 7-methylguanosine nucleoside triphosphate in 10 small capped oligoribonucleotides, releasing 5’-phosphorylated RNA fragments and 7-methylguanosine monophosphate (m7GMP). Methylations appear to have controversial roles in DCPS's cleaving efficiency where caps like tri-methyl guanosine nucleoside triphosphate (m3(2,2,7)GpppG) are cleaved with very poor efficiency and unmethylated cap analog (GpppG) witnesses no decapping activity, on mRNA molecules longer than 25 nucleotides. It does not hydrolyze 7-methylguanosine diphosphate (m7GDP) to m7GMP.
7-Methylguanosine diphosphate (m(7)GDP) is not hydrolyzed but strongly bound by decapping scavenger (dcpS) enzymes and potently inhibits their activity.
Wypijewska A., Bojarska E., Lukaszewicz M., Stepinski J., Jemielity J., Davis R.E., Darzynkiewicz E.
7-Methylguanosine diphosphate (m(7)GDP) is not hydrolyzed but strongly bound by decapping scavenger (dcpS) enzymes and potently inhibits their activity.
Coordinate expression of NADPH-dependent flavin reductase, Fre-1, and Hint-related 7meGMP-directed hydrolase, DCS-1.
DcpS can act in the 5'-3' mRNA decay pathway in addition to the 3'-5' pathway.
Functional analysis of mRNA scavenger decapping enzymes.
Functional link between the mammalian exosome and mRNA decapping.
Insights into the structure, mechanism, and regulation of scavenger mRNA decapping activity.
The scavenger mRNA decapping enzyme DcpS is a member of the HIT family of pyrophosphatases.