4pei: Difference between revisions
New page: '''Unreleased structure''' The entry 4pei is ON HOLD Authors: Montemayor, E.J., Katolik, A., Clark, N.E., Taylor, A.B., Schuermann, J.P., Combs, D.J., Johnsson, R., Holloway, S.P., Stev... |
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The | ==Dbr1 in complex with synthetic branched RNA analog== | ||
<StructureSection load='4pei' size='340' side='right'caption='[[4pei]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4pei]] is a 15 chain structure with sequence from [https://en.wikipedia.org/wiki/Entamoeba_histolytica Entamoeba histolytica] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PEI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PEI 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]] 1.95Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G46:GUANOSINE-5-MONOTHIOPHOSPHATE'>G46</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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'>[https://proteopedia.org/fgij/fg.htm?mol=4pei FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pei OCA], [https://pdbe.org/4pei PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pei RCSB], [https://www.ebi.ac.uk/pdbsum/4pei PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pei ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/C4M1P9_ENTH1 C4M1P9_ENTH1] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The enzymatic processing of cellular RNA molecules requires selective recognition of unique chemical and topological features. The unusual 2',5'-phosphodiester linkages in RNA lariats produced by the spliceosome must be hydrolyzed by the intron debranching enzyme (Dbr1) before they can be metabolized or processed into essential cellular factors, such as snoRNA and miRNA. Dbr1 is also involved in the propagation of retrotransposons and retroviruses, although the precise role played by the enzyme in these processes is poorly understood. Here, we report the first structures of Dbr1 alone and in complex with several synthetic RNA compounds that mimic the branchpoint in lariat RNA. The structures, together with functional data on Dbr1 variants, reveal the molecular basis for 2',5'-phosphodiester recognition and explain why the enzyme lacks activity toward 3',5'-phosphodiester linkages. The findings illuminate structure/function relationships in a unique enzyme that is central to eukaryotic RNA metabolism and set the stage for the rational design of inhibitors that may represent novel therapeutic agents to treat retroviral infections and neurodegenerative disease. | |||
Structural basis of lariat RNA recognition by the intron debranching enzyme Dbr1.,Montemayor EJ, Katolik A, Clark NE, Taylor AB, Schuermann JP, Combs DJ, Johnsson R, Holloway SP, Stevens SW, Damha MJ, Hart PJ Nucleic Acids Res. 2014 Aug 14. pii: gku725. PMID:25123664<ref>PMID:25123664</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4pei" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Entamoeba histolytica]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Clark NE]] | |||
[[Category: Combs DJ]] | |||
[[Category: Damha MJ]] | |||
[[Category: Hart PJ]] | |||
[[Category: Holloway SP]] | |||
[[Category: Johnsson R]] | |||
[[Category: Katolik A]] | |||
[[Category: Montemayor EJ]] | |||
[[Category: Schuermann JP]] | |||
[[Category: Stevens SW]] | |||
[[Category: Taylor AB]] | |||
Latest revision as of 03:43, 28 December 2023
Dbr1 in complex with synthetic branched RNA analogDbr1 in complex with synthetic branched RNA analog
Structural highlights
FunctionPublication Abstract from PubMedThe enzymatic processing of cellular RNA molecules requires selective recognition of unique chemical and topological features. The unusual 2',5'-phosphodiester linkages in RNA lariats produced by the spliceosome must be hydrolyzed by the intron debranching enzyme (Dbr1) before they can be metabolized or processed into essential cellular factors, such as snoRNA and miRNA. Dbr1 is also involved in the propagation of retrotransposons and retroviruses, although the precise role played by the enzyme in these processes is poorly understood. Here, we report the first structures of Dbr1 alone and in complex with several synthetic RNA compounds that mimic the branchpoint in lariat RNA. The structures, together with functional data on Dbr1 variants, reveal the molecular basis for 2',5'-phosphodiester recognition and explain why the enzyme lacks activity toward 3',5'-phosphodiester linkages. The findings illuminate structure/function relationships in a unique enzyme that is central to eukaryotic RNA metabolism and set the stage for the rational design of inhibitors that may represent novel therapeutic agents to treat retroviral infections and neurodegenerative disease. Structural basis of lariat RNA recognition by the intron debranching enzyme Dbr1.,Montemayor EJ, Katolik A, Clark NE, Taylor AB, Schuermann JP, Combs DJ, Johnsson R, Holloway SP, Stevens SW, Damha MJ, Hart PJ Nucleic Acids Res. 2014 Aug 14. pii: gku725. PMID:25123664[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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