9d5k

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Current revision (08:15, 6 November 2024) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 9d5k is ON HOLD
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==Human Adenosine Deaminase Acting on dsRNA (ADAR2-RD) bound to dsRNA containing an expanded cytidine analog at the -1 position of the guide strand==
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<StructureSection load='9d5k' size='340' side='right'caption='[[9d5k]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[9d5k]] is a 4 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=9D5K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9D5K 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]] 2.697&#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=8AZ:8-AZA-NEBULARINE-5-MONOPHOSPHATE'>8AZ</scene>, <scene name='pdbligand=A1BBA:(1R)-1-(2-amino-8-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)-1,4-anhydro-2-deoxy-5-O-phosphono-D-erythro-pentitol'>A1BBA</scene>, <scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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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=9d5k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9d5k OCA], [https://pdbe.org/9d5k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9d5k RCSB], [https://www.ebi.ac.uk/pdbsum/9d5k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9d5k ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/RED1_HUMAN RED1_HUMAN] Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2 and GRIK2) and serotonin (HTR2C), GABA receptor (GABRA3) and potassium voltage-gated channel (KCNA1). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alter their functional activities. Edits GRIA2 at both the Q/R and R/G sites efficiently but converts the adenosine in hotspot1 much less efficiently. Can exert a proviral effect towards human immunodeficiency virus type 1 (HIV-1) and enhances its replication via both an editing-dependent and editing-independent mechanism. The former involves editing of adenosines in the 5'UTR while the latter occurs via suppression of EIF2AK2/PKR activation and function. Can inhibit cell proliferation and migration and can stimulate exocytosis.<ref>PMID:18178553</ref> <ref>PMID:19908260</ref> <ref>PMID:21289159</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Adenosine Deaminases Acting on RNA (ADARs) are members of a family of RNA editing enzymes that catalyze the conversion of adenosine into inosine in double-stranded RNA (dsRNA). ADARs' selective activity on dsRNA presents the ability to correct mutations at the transcriptome level using guiding oligonucleotides. However, this approach is limited by ADARs' preference for specific sequence contexts to achieve efficient editing. Substrates with a guanosine adjacent to the target adenosine in the 5' direction (5'-GA) are edited less efficiently compared to substrates with any other canonical nucleotides at this position. Previous studies showed that a G/purine mismatch at this position results in more efficient editing than a canonical G/C pair. Herein, we investigate a series of modified oligonucleotides containing purine or size-expanded nucleoside analogs on guide strands opposite the 5'-G (-1 position). The results demonstrate that modified adenosine and inosine analogs enhance editing at 5'-GA sites. Additionally, the inclusion of a size-expanded cytidine analog at this position improves editing over a control guide bearing cytidine. High-resolution crystal structures of ADAR:/RNA substrate complexes reveal the manner by which both inosine and size-expanded cytidine are capable of activating editing at 5'-GA sites. Further modification of these altered guide sequences for metabolic stability in human cells demonstrates that the incorporation of specific purine analogs at the -1 position significantly improves editing at 5'-GA sites.
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Authors: Fisher, A.J., Cheng, J., Manjunath, A., Campbell, K.
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Nucleoside Analogs in ADAR Guide Strands Enable Editing at 5'-GA Sites.,Manjunath A, Cheng J, Campbell KB, Jacobsen CS, Mendoza HG, Bierbaum L, Jauregui-Matos V, Doherty EE, Fisher AJ, Beal PA Biomolecules. 2024 Sep 29;14(10):1229. doi: 10.3390/biom14101229. PMID:39456162<ref>PMID:39456162</ref>
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Description: Human Adenosine Deaminase Acting on dsRNA (ADAR2-RD) bound to dsRNA containing an expanded cytidine analog at the -1 position of the guide strand
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Cheng, J]]
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<div class="pdbe-citations 9d5k" style="background-color:#fffaf0;"></div>
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[[Category: Manjunath, A]]
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== References ==
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[[Category: Fisher, A.J]]
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<references/>
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[[Category: Campbell, K]]
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Campbell K]]
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[[Category: Cheng J]]
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[[Category: Fisher AJ]]
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[[Category: Manjunath A]]

Current revision

Human Adenosine Deaminase Acting on dsRNA (ADAR2-RD) bound to dsRNA containing an expanded cytidine analog at the -1 position of the guide strand

PDB ID 9d5k

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