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- | {{STRUCTURE_1st0| PDB=1st0 | SCENE= }} | |
- | ===Structure of DcpS bound to m7GpppG=== | |
- | {{ABSTRACT_PUBMED_15068804}} | |
| | | |
- | ==Function== | + | ==Structure of DcpS bound to m7GpppG== |
- | [[http://www.uniprot.org/uniprot/DCPS_HUMAN 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.<ref>PMID:12198172</ref> <ref>PMID:12871939</ref> <ref>PMID:11747811</ref> <ref>PMID:14523240</ref> <ref>PMID:15273322</ref> <ref>PMID:15383679</ref> <ref>PMID:16140270</ref> <ref>PMID:18426921</ref> <ref>PMID:22985415</ref> <ref>PMID:15769464</ref> | + | <StructureSection load='1st0' size='340' side='right'caption='[[1st0]], [[Resolution|resolution]] 1.90Å' scene=''> |
- | | + | == Structural highlights == |
- | ==About this Structure== | + | <table><tr><td colspan='2'>[[1st0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The February 2007 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Exosomes'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2007_2 10.2210/rcsb_pdb/mom_2007_2]. The January 2012 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Messenger RNA Capping'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2012_1 10.2210/rcsb_pdb/mom_2012_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ST0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ST0 FirstGlance]. <br> |
- | [[1st0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The February 2007 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Exosomes'' by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2007_2 10.2210/rcsb_pdb/mom_2007_2]. The January 2012 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Messenger RNA Capping'' by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2012_1 10.2210/rcsb_pdb/mom_2012_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ST0 OCA]. | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
- | | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTG:7-METHYL-GUANOSINE-5-TRIPHOSPHATE-5-GUANOSINE'>GTG</scene>, <scene name='pdbligand=YT3:YTTRIUM+(III)+ION'>YT3</scene></td></tr> |
- | ==Reference==
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1st0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1st0 OCA], [https://pdbe.org/1st0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1st0 RCSB], [https://www.ebi.ac.uk/pdbsum/1st0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1st0 ProSAT]</span></td></tr> |
- | <ref group="xtra">PMID:015068804</ref><references group="xtra"/><references/> | + | </table> |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/DCPS_HUMAN 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.<ref>PMID:12198172</ref> <ref>PMID:12871939</ref> <ref>PMID:11747811</ref> <ref>PMID:14523240</ref> <ref>PMID:15273322</ref> <ref>PMID:15383679</ref> <ref>PMID:16140270</ref> <ref>PMID:18426921</ref> <ref>PMID:22985415</ref> <ref>PMID:15769464</ref> |
| + | == Evolutionary Conservation == |
| + | [[Image:Consurf_key_small.gif|200px|right]] |
| + | Check<jmol> |
| + | <jmolCheckbox> |
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/st/1st0_consurf.spt"</scriptWhenChecked> |
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| + | <text>to colour the structure by Evolutionary Conservation</text> |
| + | </jmolCheckbox> |
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1st0 ConSurf]. |
| + | <div style="clear:both"></div> |
| + | == References == |
| + | <references/> |
| + | __TOC__ |
| + | </StructureSection> |
| [[Category: Exosomes]] | | [[Category: Exosomes]] |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| + | [[Category: Large Structures]] |
| [[Category: Messenger RNA Capping]] | | [[Category: Messenger RNA Capping]] |
| [[Category: RCSB PDB Molecule of the Month]] | | [[Category: RCSB PDB Molecule of the Month]] |
- | [[Category: Fabrega, C.]] | + | [[Category: Fabrega C]] |
- | [[Category: Gu, M.]] | + | [[Category: Gu M]] |
- | [[Category: Kiledjian, M.]] | + | [[Category: Kiledjian M]] |
- | [[Category: Lima, C D.]] | + | [[Category: Lima CD]] |
- | [[Category: Liu, H.]] | + | [[Category: Liu H]] |
- | [[Category: Liu, S W.]] | + | [[Category: Liu SW]] |
- | [[Category: Cap]]
| + | |
- | [[Category: Decapping]]
| + | |
- | [[Category: Exosome]]
| + | |
- | [[Category: Hit protein]]
| + | |
- | [[Category: Messenger rna]]
| + | |
- | [[Category: Mrna]]
| + | |
- | [[Category: Rna binding protein]]
| + | |
- | [[Category: Rna decay]]
| + | |
| Structural highlights
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.
References
- ↑ 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
- ↑ 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
- ↑ Wang Z, Kiledjian M. Functional link between the mammalian exosome and mRNA decapping. Cell. 2001 Dec 14;107(6):751-62. PMID:11747811
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
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