View source for 5hp2


==Human Adenosine Deaminase Acting on dsRNA (ADAR2) bound to dsRNA sequence derived from S. cerevisiae BDF2 gene with AU basepair at reaction site==
<StructureSection load='5hp2' size='340' side='right' caption='[[5hp2]], [[Resolution|resolution]] 2.98&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5hp2]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HP2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HP2 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=8AZ:8-AZA-NEBULARINE-5-MONOPHOSPHATE'>8AZ</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ed1|5ed1]], [[5ed2|5ed2]], [[5hp3|5hp3]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Double-stranded_RNA_adenine_deaminase Double-stranded RNA adenine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.37 3.5.4.37] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5hp2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hp2 OCA], [http://pdbe.org/5hp2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hp2 RCSB], [http://www.ebi.ac.uk/pdbsum/5hp2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hp2 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Adenosine deaminases acting on RNA (ADARs) are editing enzymes that convert adenosine to inosine in duplex RNA, a modification reaction with wide-ranging consequences in RNA function. Understanding of the ADAR reaction mechanism, the origin of editing-site selectivity, and the effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. Here we describe four crystal structures of the human ADAR2 deaminase domain bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis of the ADAR deaminase domain's dsRNA specificity, its base-flipping mechanism, and its nearest-neighbor preferences. In addition, we identified an ADAR2-specific RNA-binding loop near the enzyme active site, thus rationalizing differences in selectivity observed between different ADARs. Finally, our results provide a structural framework for understanding the effects of ADAR mutations associated with human disease.

Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity.,Matthews MM, Thomas JM, Zheng Y, Tran K, Phelps KJ, Scott AI, Havel J, Fisher AJ, Beal PA Nat Struct Mol Biol. 2016 May;23(5):426-33. doi: 10.1038/nsmb.3203. Epub 2016 Apr, 11. PMID:27065196<ref>PMID:27065196</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5hp2" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Double-stranded RNA adenine deaminase]]
[[Category: Beal, P A]]
[[Category: Fisher, A J]]
[[Category: Matthews, M M]]
[[Category: Deaminase]]
[[Category: Human]]
[[Category: Hydrolase-rna complex]]