1st4: Difference between revisions

New page: left|200px<br /> <applet load="1st4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1st4, resolution 2.02Å" /> '''Structure of DcpS b...
 
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[[Image:1st4.gif|left|200px]]<br />
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'''Structure of DcpS bound to m7GpppA'''<br />


==Overview==
==Structure of DcpS bound to m7GpppA==
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.
<StructureSection load='1st4' size='340' side='right'caption='[[1st4]], [[Resolution|resolution]] 2.02&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1st4]] is a 2 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=1ST4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ST4 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.02&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTA:P1-7-METHYLGUANOSINE-P3-ADENOSINE-5,5-TRIPHOSPHATE'>GTA</scene>, <scene name='pdbligand=YT3:YTTRIUM+(III)+ION'>YT3</scene></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=1st4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1st4 OCA], [https://pdbe.org/1st4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1st4 RCSB], [https://www.ebi.ac.uk/pdbsum/1st4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1st4 ProSAT]</span></td></tr>
</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/1st4_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=1st4 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


==About this Structure==
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<ref>PMID:15068804</ref>
1ST4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with YT3 and GTA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ST4 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15068804 15068804]
</div>
<div class="pdbe-citations 1st4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[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: GTA]]
[[Category: YT3]]
[[Category: cap]]
[[Category: decapping]]
[[Category: exosome]]
[[Category: hit protein]]
[[Category: messenger rna]]
[[Category: mrna]]
[[Category: rna decay]]
 
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