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| | <StructureSection load='4qeb' size='340' side='right'caption='[[4qeb]], [[Resolution|resolution]] 3.21Å' scene=''> | | <StructureSection load='4qeb' size='340' side='right'caption='[[4qeb]], [[Resolution|resolution]] 3.21Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qeb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QEB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QEB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qeb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QEB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QEB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=31G:3-{[(2,4-DIAMINOQUINAZOLIN-5-YL)OXY]METHYL}BENZENESULFONIC+ACID'>31G</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=31G:3-{[(2,4-DIAMINOQUINAZOLIN-5-YL)OXY]METHYL}BENZENESULFONIC+ACID'>31G</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qde|4qde]], [[4qdv|4qdv]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4qeb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qeb OCA], [https://pdbe.org/4qeb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qeb RCSB], [https://www.ebi.ac.uk/pdbsum/4qeb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qeb ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DCPS, DCS1, HINT5, HSPC015 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/5'-(N(7)-methyl_5'-triphosphoguanosine)-(mRNA)_diphosphatase 5'-(N(7)-methyl 5'-triphosphoguanosine)-(mRNA) diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.59 3.6.1.59] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qeb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qeb OCA], [http://pdbe.org/4qeb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qeb RCSB], [http://www.ebi.ac.uk/pdbsum/4qeb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qeb ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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> | + | [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> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Liu, S]] | + | [[Category: Liu S]] |
| - | [[Category: 3'->5' exosome-mediated mrna decay pathway]]
| + | |
| - | [[Category: Decapping scavenger enzyme]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Mrna degradation]]
| + | |
| - | [[Category: Residual cap structure cleavage]]
| + | |
| 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]
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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