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1st0

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Structure of DcpS bound to m7GpppGStructure of DcpS bound to m7GpppG

Structural highlights

1st0 is a 2 chain structure with sequence from Human. The February 2007 RCSB PDB Molecule of the Month feature on Exosomes by David S. Goodsell is 10.2210/rcsb_pdb/mom_2007_2. The January 2012 RCSB PDB Molecule of the Month feature on Messenger RNA Capping by David Goodsell is 10.2210/rcsb_pdb/mom_2012_1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:,
Gene:DCPS (HUMAN)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DCPS_HUMAN] 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) with up to 10 nucleotide substrates (small capped oligoribonucleotides) and specifically releases 5'-phosphorylated RNA fragments and 7-methylguanosine monophosphate (m7GMP). Cleaves cap analog structures like tri-methyl guanosine nucleoside triphosphate (m3(2,2,7)GpppG) with very poor efficiency. 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) to m7GMP (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 DCPS to m7GMP (PubMed:14523240). Binds to m7GpppG and strongly to m7GDP. Plays a role in first intron splicing of pre-mRNAs. Inhibits activation-induced cell death.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]

Evolutionary Conservation

 

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Insights into the structure, mechanism, and regulation of scavenger mRNA decapping activity.,Gu M, Fabrega C, Liu SW, Liu H, Kiledjian M, Lima CD Mol Cell. 2004 Apr 9;14(1):67-80. PMID:15068804[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Liu H, Rodgers ND, Jiao X, Kiledjian M. The scavenger mRNA decapping enzyme DcpS is a member of the HIT family of pyrophosphatases. EMBO J. 2002 Sep 2;21(17):4699-708. PMID:12198172
  2. ↑ Kwasnicka DA, Krakowiak A, Thacker C, Brenner C, Vincent SR. Coordinate expression of NADPH-dependent flavin reductase, Fre-1, and Hint-related 7meGMP-directed hydrolase, DCS-1. J Biol Chem. 2003 Oct 3;278(40):39051-8. Epub 2003 Jul 18. PMID:12871939 doi:http://dx.doi.org/10.1074/jbc.M306355200
  3. ↑ Wang Z, Kiledjian M. Functional link between the mammalian exosome and mRNA decapping. Cell. 2001 Dec 14;107(6):751-62. PMID:11747811
  4. ↑ van Dijk E, Le Hir H, Seraphin B. DcpS can act in the 5'-3' mRNA decay pathway in addition to the 3'-5' pathway. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12081-6. Epub 2003 Oct 1. PMID:14523240 doi:http://dx.doi.org/10.1073/pnas.1635192100
  5. ↑ Liu SW, Jiao X, Liu H, Gu M, Lima CD, Kiledjian M. Functional analysis of mRNA scavenger decapping enzymes. RNA. 2004 Sep;10(9):1412-22. Epub 2004 Jul 23. PMID:15273322 doi:http://dx.doi.org/10.1261/rna.7660804
  6. ↑ Cohen LS, Mikhli C, Friedman C, Jankowska-Anyszka M, Stepinski J, Darzynkiewicz E, Davis RE. Nematode m7GpppG and m3(2,2,7)GpppG decapping: activities in Ascaris embryos and characterization of C. elegans scavenger DcpS. RNA. 2004 Oct;10(10):1609-24. PMID:15383679 doi:http://dx.doi.org/10.1261/rna.7690504
  7. ↑ Kwasnicka-Crawford DA, Vincent SR. Role of a novel dual flavin reductase (NR1) and an associated histidine triad protein (DCS-1) in menadione-induced cytotoxicity. Biochem Biophys Res Commun. 2005 Oct 21;336(2):565-71. PMID:16140270 doi:http://dx.doi.org/S0006-291X(05)01784-5
  8. ↑ Shen V, Liu H, Liu SW, Jiao X, Kiledjian M. DcpS scavenger decapping enzyme can modulate pre-mRNA splicing. RNA. 2008 Jun;14(6):1132-42. doi: 10.1261/rna.1008208. Epub 2008 Apr 21. PMID:18426921 doi:http://dx.doi.org/10.1261/rna.1008208
  9. ↑ Wypijewska A, Bojarska E, Lukaszewicz M, Stepinski J, Jemielity J, Davis RE, Darzynkiewicz E. 7-methylguanosine diphosphate (m(7)GDP) is not hydrolyzed but strongly bound by decapping scavenger (DcpS) enzymes and potently inhibits their activity. Biochemistry. 2012 Oct 9;51(40):8003-13. doi: 10.1021/bi300781g. Epub 2012 Sep, 25. PMID:22985415 doi:http://dx.doi.org/10.1021/bi300781g
  10. ↑ Chen N, Walsh MA, Liu Y, Parker R, Song H. Crystal structures of human DcpS in ligand-free and m7GDP-bound forms suggest a dynamic mechanism for scavenger mRNA decapping. J Mol Biol. 2005 Apr 8;347(4):707-18. PMID:15769464 doi:10.1016/j.jmb.2005.01.062
  11. ↑ Gu M, Fabrega C, Liu SW, Liu H, Kiledjian M, Lima CD. Insights into the structure, mechanism, and regulation of scavenger mRNA decapping activity. Mol Cell. 2004 Apr 9;14(1):67-80. PMID:15068804

1st0, resolution 1.90Å

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