3bl9

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{{Seed}}
 
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[[Image:3bl9.png|left|200px]]
 
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==Synthetic Gene Encoded DcpS bound to inhibitor DG157493==
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The line below this paragraph, containing "STRUCTURE_3bl9", creates the "Structure Box" on the page.
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<StructureSection load='3bl9' size='340' side='right'caption='[[3bl9]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3bl9]] 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=3BL9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BL9 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DD2:5-{[1-(2,3-DICHLOROBENZYL)PIPERIDIN-4-YL]METHOXY}QUINAZOLINE-2,4-DIAMINE'>DD2</scene></td></tr>
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{{STRUCTURE_3bl9| PDB=3bl9 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bl9 OCA], [https://pdbe.org/3bl9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bl9 RCSB], [https://www.ebi.ac.uk/pdbsum/3bl9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bl9 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bl/3bl9_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=3bl9 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Spinal muscular atrophy (SMA) is caused by deletion or mutation of both copies of the SMN1 gene, which produces an essential protein known as SMN. The severity of SMA is modified by variable copy number of a second gene, SMN2, which produces an mRNA that is incorrectly spliced with deletion of the last exon. We described previously the discovery of potent C5-substituted quinazolines that increase SMN2 gene expression by 2-fold. Discovery of potent SMN2 promoter inducers relied on a cellular assay without knowledge of the molecular target. Using protein microarray scanning with a radiolabeled C5-substituted quinazoline probe, we identified the scavenger decapping enzyme, DcpS, as a potential binder. We show that the C5-substituted quinazolines potently inhibit DcpS decapping activity and that the potency of inhibition correlates with potency for SMN2 promoter induction. Binding of C5-substituted quinazolines to DcpS holds the enzyme in an open, catalytically incompetent conformation. DcpS is a nuclear shuttling protein that binds and hydrolyzes the m (7)GpppN mRNA cap structure and a modulator of RNA metabolism. Therefore DcpS represents a novel therapeutic target for modulating gene expression by a small molecule.
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===Synthetic Gene Encoded DcpS bound to inhibitor DG157493===
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DcpS as a Therapeutic Target for Spinal Muscular Atrophy.,Singh J, Salcius M, Liu SW, Staker BL, Mishra R, Thurmond J, Michaud G, Mattoon DR, Printen J, Christensen J, Bjornsson JM, Pollok BA, Kiledjian M, Stewart L, Jarecki J, Gurney ME ACS Chem Biol. 2008 Oct 8. PMID:18839960<ref>PMID:18839960</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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The line below this paragraph, {{ABSTRACT_PUBMED_18839960}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 3bl9" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 18839960 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_18839960}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3BL9 is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BL9 OCA].
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==Reference==
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<ref group="xtra">PMID:18839960</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: ATCG3D, Accelerated Technologies Center for Gene to 3D Structure.]]
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[[Category: Large Structures]]
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[[Category: Christensen, J.]]
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[[Category: Christensen J]]
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[[Category: Staker, B L.]]
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[[Category: Staker BL]]
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[[Category: Stewart, L.]]
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[[Category: Stewart L]]
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[[Category: Accelerated technologies center for gene to 3d structure]]
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[[Category: Atcg3d]]
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[[Category: Cytoplasm]]
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[[Category: Dcp]]
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[[Category: Hydrolase]]
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[[Category: Ligand complex]]
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[[Category: Mrna decapping enzyme]]
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[[Category: Nonsense-mediated mrna decay]]
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[[Category: Nucleus]]
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[[Category: Polymorphism]]
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[[Category: Protein structure initiative]]
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[[Category: Psi-2]]
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[[Category: Structural genomic]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 7 13:25:26 2009''
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Current revision

Synthetic Gene Encoded DcpS bound to inhibitor DG157493

PDB ID 3bl9

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OCA

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