6aiy

From Proteopedia

(Difference between revisions)

Revision as of 11:37, 23 March 2022

Crystal structure of DXO (E234A mutant) in complex with adenosine 3', 5' bisphosphate and two magnesium ions

Structural highlights

6aiy is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	6aix
Gene:	Dxo, Dom3z, Ng6 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DXO_MOUSE] Ribonuclease that specifically degrades pre-mRNAs with a defective 5' end cap and is part of a pre-mRNA capping quality control. Has decapping, pyrophosphohydrolase and 5'-3' exonuclease activities. Has decapping activity toward incomplete 5' end cap mRNAs such as unmethylated 5' end-capped RNA to release GpppN and 5' end monophosphate RNA. The 5' end monophosphate RNA is then degraded by the 5'-3' exoribonuclease activity, enabling this enzyme to decap and degrade incompletely capped mRNAs. Also possesses RNA 5'-pyrophosphohydrolase activity by hydrolyzing the 5' end triphosphate to release pyrophosphates.^[1]

Publication Abstract from PubMed

The decapping exoribonuclease DXO functions in pre-mRNA capping quality control, and shows multiple biochemical activities such as decapping, deNADding, pyrophosphohydrolase, and 5'-3' exoribonuclease activities. Previous studies revealed the molecular mechanisms of DXO based on the structures in complexes with a product, substrate mimic, cap analogue, and 3'-NADP(+). Despite several reports on the substrate-specific reaction mechanism, the inhibitory mechanism of DXO remains elusive. Here, we demonstrate that adenosine 3', 5'-bisphosphate (pAp), a known inhibitor of the 5'-3' exoribonuclease Xrn1, inhibits the nuclease activity of DXO based on the results of structural and biochemical experiments. We determined the crystal structure of the DXO-pAp-Mg(2+) complex at 1.8A resolution. In comparison with the DXO-RNA product complex, the position of pAp is well superimposed with the first nucleotide of the product RNA in the vicinity of two magnesium ions. Furthermore, biochemical assays showed that the inhibition by pAp is comparable between Xrn1 and DXO. Collectively, these structural and biochemical studies reveal that pAp inhibits the activities of DXO by occupying the active site to act as a competitive inhibitor.

Molecular mechanism for the inhibition of DXO by adenosine 3',5'-bisphosphate.,Yun JS, Yoon JH, Choi YJ, Son YJ, Kim S, Tong L, Chang JH Biochem Biophys Res Commun. 2018 Sep 26;504(1):89-95. doi:, 10.1016/j.bbrc.2018.08.135. Epub 2018 Sep 1. PMID:30180947^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Jiao X, Chang JH, Kilic T, Tong L, Kiledjian M. A mammalian pre-mRNA 5' end capping quality control mechanism and an unexpected link of capping to pre-mRNA processing. Mol Cell. 2013 Apr 11;50(1):104-15. doi: 10.1016/j.molcel.2013.02.017. Epub 2013 , Mar 21. PMID:23523372 doi:http://dx.doi.org/10.1016/j.molcel.2013.02.017
↑ Yun JS, Yoon JH, Choi YJ, Son YJ, Kim S, Tong L, Chang JH. Molecular mechanism for the inhibition of DXO by adenosine 3',5'-bisphosphate. Biochem Biophys Res Commun. 2018 Sep 26;504(1):89-95. doi:, 10.1016/j.bbrc.2018.08.135. Epub 2018 Sep 1. PMID:30180947 doi:http://dx.doi.org/10.1016/j.bbrc.2018.08.135

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6aiy"

@@ Line 3: / Line 3: @@
 <StructureSection load='6aiy' size='340' side='right'caption='[[6aiy]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6aiy]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AIY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6AIY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6aiy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AIY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AIY FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A3P:ADENOSINE-3-5-DIPHOSPHATE'>A3P</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6aix|6aix]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6aix|6aix]]</div></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6aiy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aiy OCA], [http://pdbe.org/6aiy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aiy RCSB], [http://www.ebi.ac.uk/pdbsum/6aiy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aiy ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dxo, Dom3z, Ng6 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=6aiy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aiy OCA], [https://pdbe.org/6aiy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aiy RCSB], [https://www.ebi.ac.uk/pdbsum/6aiy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aiy ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/DXO_MOUSE DXO_MOUSE]] Ribonuclease that specifically degrades pre-mRNAs with a defective 5' end cap and is part of a pre-mRNA capping quality control. Has decapping, pyrophosphohydrolase and 5'-3' exonuclease activities. Has decapping activity toward incomplete 5' end cap mRNAs such as unmethylated 5' end-capped RNA to release GpppN and 5' end monophosphate RNA. The 5' end monophosphate RNA is then degraded by the 5'-3' exoribonuclease activity, enabling this enzyme to decap and degrade incompletely capped mRNAs. Also possesses RNA 5'-pyrophosphohydrolase activity by hydrolyzing the 5' end triphosphate to release pyrophosphates.<ref>PMID:23523372</ref>
+[[https://www.uniprot.org/uniprot/DXO_MOUSE DXO_MOUSE]] Ribonuclease that specifically degrades pre-mRNAs with a defective 5' end cap and is part of a pre-mRNA capping quality control. Has decapping, pyrophosphohydrolase and 5'-3' exonuclease activities. Has decapping activity toward incomplete 5' end cap mRNAs such as unmethylated 5' end-capped RNA to release GpppN and 5' end monophosphate RNA. The 5' end monophosphate RNA is then degraded by the 5'-3' exoribonuclease activity, enabling this enzyme to decap and degrade incompletely capped mRNAs. Also possesses RNA 5'-pyrophosphohydrolase activity by hydrolyzing the 5' end triphosphate to release pyrophosphates.<ref>PMID:23523372</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 25: @@
 </StructureSection>
 [[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Chang, J H]]
 [[Category: Tong, L]]

6aiy

From Proteopedia

Revision as of 11:37, 23 March 2022

Crystal structure of DXO (E234A mutant) in complex with adenosine 3', 5' bisphosphate and two magnesium ions

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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