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| | ==Yeast Scavenger Decapping Enzyme in complex with m7GDP== | | ==Yeast Scavenger Decapping Enzyme in complex with m7GDP== |
| - | <StructureSection load='5bv3' size='340' side='right' caption='[[5bv3]], [[Resolution|resolution]] 2.25Å' scene=''> | + | <StructureSection load='5bv3' size='340' side='right'caption='[[5bv3]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5bv3]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BV3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BV3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5bv3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BV3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BV3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=M7G:7N-METHYL-8-HYDROGUANOSINE-5-DIPHOSPHATE'>M7G</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=M7G:7N-METHYL-8-HYDROGUANOSINE-5-DIPHOSPHATE'>M7G</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5bv3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bv3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5bv3 RCSB], [http://www.ebi.ac.uk/pdbsum/5bv3 PDBsum]</span></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=5bv3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bv3 OCA], [https://pdbe.org/5bv3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bv3 RCSB], [https://www.ebi.ac.uk/pdbsum/5bv3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bv3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DCPS_YEAST DCPS_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.<ref>PMID:12198172</ref> <ref>PMID:14523240</ref> <ref>PMID:15240832</ref> <ref>PMID:15273322</ref> <ref>PMID:16260594</ref> <ref>PMID:16963086</ref> <ref>PMID:22985415</ref> | + | [https://www.uniprot.org/uniprot/DCPS_YEAST DCPS_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.<ref>PMID:12198172</ref> <ref>PMID:14523240</ref> <ref>PMID:15240832</ref> <ref>PMID:15273322</ref> <ref>PMID:16260594</ref> <ref>PMID:16963086</ref> <ref>PMID:22985415</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 5bv3" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Neu, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Neu, U]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Sprangers, R]] | + | [[Category: Neu A]] |
| - | [[Category: Cap structure]] | + | [[Category: Neu U]] |
| - | [[Category: Decapping enzyme]] | + | [[Category: Sprangers R]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Protein dynamic]]
| + | |
| - | [[Category: Scavenger decapping enzyme]]
| + | |
| - | [[Category: Substrate inhibition]]
| + | |
| Structural highlights
Function
DCPS_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 PubMed
The 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
- ↑ 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
- ↑ 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
- ↑ Malys N, Carroll K, Miyan J, Tollervey D, McCarthy JE. The 'scavenger' m7GpppX pyrophosphatase activity of Dcs1 modulates nutrient-induced responses in yeast. Nucleic Acids Res. 2004 Jul 7;32(12):3590-600. Print 2004. PMID:15240832 doi:http://dx.doi.org/10.1093/nar/gkh687
- ↑ 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
- ↑ Liu H, Kiledjian M. Scavenger decapping activity facilitates 5' to 3' mRNA decay. Mol Cell Biol. 2005 Nov;25(22):9764-72. PMID:16260594 doi:http://dx.doi.org/10.1128/MCB.25.22.9764-9772.2005
- ↑ Malys N, McCarthy JE. Dcs2, a novel stress-induced modulator of m7GpppX pyrophosphatase activity that locates to P bodies. J Mol Biol. 2006 Oct 20;363(2):370-82. Epub 2006 Aug 11. PMID:16963086 doi:http://dx.doi.org/10.1016/j.jmb.2006.08.015
- ↑ 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
- ↑ Neu A, Neu U, Fuchs AL, Schlager B, Sprangers R. An excess of catalytically required motions inhibits the scavenger decapping enzyme. Nat Chem Biol. 2015 Sep;11(9):697-704. doi: 10.1038/nchembio.1866. Epub 2015 Aug , 10. PMID:26258763 doi:http://dx.doi.org/10.1038/nchembio.1866
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