View source for 3irr


==Crystal Structure of a Z-Z junction (with HEPES intercalating)==
<StructureSection load='3irr' size='340' side='right' caption='[[3irr]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3irr]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IRR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3IRR FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1qbj|1qbj]], [[3irq|3irq]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADAR, ADAR1, DSRAD, G1P1, IFI4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3irr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3irr OCA], [http://pdbe.org/3irr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3irr RCSB], [http://www.ebi.ac.uk/pdbsum/3irr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3irr ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/DSRAD_HUMAN DSRAD_HUMAN]] Defects in ADAR are a cause of dyschromatosis symmetrical hereditaria (DSH) [MIM:[http://omim.org/entry/127400 127400]]; also known as reticulate acropigmentation of Dohi. DSH is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal parts of the hands and feet.<ref>PMID:12916015</ref> <ref>PMID:15146470</ref> <ref>PMID:15659327</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/DSRAD_HUMAN DSRAD_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 serotonin (HTR2C) and GABA receptor (GABRA3). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alters their functional activities. Exhibits low-level editing at the GRIA2 Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Its viral RNA substrates include: hepatitis C virus (HCV), vesicular stomatitis virus (VSV), measles virus (MV), hepatitis delta virus (HDV), and human immunodeficiency virus type 1 (HIV-1). Exhibits either a proviral (HDV, MV, VSV and HIV-1) or an antiviral effect (HCV) and this can be editing-dependent (HDV and HCV), editing-independent (VSV and MV) or both (HIV-1). Impairs HCV replication via RNA editing at multiple sites. Enhances the replication of MV, VSV and HIV-1 through an editing-independent mechanism via suppression of EIF2AK2/PKR activation and function. Stimulates both the release and infectivity of HIV-1 viral particles by an editing-dependent mechanism where it associates with viral RNAs and edits adenosines in the 5'UTR and the Rev and Tat coding sequence. Can enhance viral replication of HDV via A-to-I editing at a site designated as amber/W, thereby changing an UAG amber stop codon to an UIG tryptophan (W) codon that permits synthesis of the large delta antigen (L-HDAg) which has a key role in the assembly of viral particles. However, high levels of ADAR1 inhibit HDV replication.<ref>PMID:15556947</ref> <ref>PMID:15858013</ref> <ref>PMID:16475990</ref> <ref>PMID:17079286</ref> <ref>PMID:19710021</ref> <ref>PMID:19605474</ref> <ref>PMID:19651874</ref> <ref>PMID:19908260</ref> <ref>PMID:21289159</ref> <ref>PMID:22278222</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ir/3irr_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=3irr ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The double helix of DNA, when composed of dinucleotide purine-pyrimidine repeats, can adopt a left-handed helical structure called Z-DNA. For reasons not entirely understood, such dinucleotide repeats in genomic sequences have been associated with genomic instability leading to cancer. Adoption of the left-handed conformation results in the formation of conformational junctions: A B-to-Z junction is formed at the boundaries of the helix, whereas a Z-to-Z junction is commonly formed in sequences where the dinucleotide repeat is interrupted by single base insertions or deletions that bring neighboring helices out of phase. B-Z junctions are shown to result in exposed nucleotides vulnerable to chemical or enzymatic modification. Here we describe the three-dimensional structure of a Z-Z junction stabilized by Zalpha, the Z-DNA binding domain of the RNA editing enzyme ADAR1. We show that the junction structure consists of a single base pair and leads to partial or full disruption of the helical stacking. The junction region allows intercalating agents to insert themselves into the left-handed helix, which is otherwise resistant to intercalation. However, unlike a B-Z junction, in this structure the bases are not fully extruded, and the stacking between the two left-handed helices is not continuous.

Crystal structure of a junction between two Z-DNA helices.,de Rosa M, de Sanctis D, Rosario AL, Archer M, Rich A, Athanasiadis A, Carrondo MA Proc Natl Acad Sci U S A. 2010 May 3. PMID:20439751<ref>PMID:20439751</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3irr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Adenosine deaminase|Adenosine deaminase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Athanasiadis, A]]
[[Category: Rosa, M de]]
[[Category: Adar1]]
[[Category: Alternative promoter usage]]
[[Category: Alternative splicing]]
[[Category: Cytoplasm]]
[[Category: Disease mutation]]
[[Category: Dna junction]]
[[Category: Dna-binding]]
[[Category: Hydrolase]]
[[Category: Hydrolase-dna complex]]
[[Category: Innate immunity]]
[[Category: Intercalation]]
[[Category: Isopeptide bond]]
[[Category: Metal-binding]]
[[Category: Mrna processing]]
[[Category: Nucleus]]
[[Category: Phosphoprotein]]
[[Category: Polymorphism]]
[[Category: Rna editing]]
[[Category: Rna-binding]]
[[Category: Rna-mediated gene silencing]]
[[Category: Ubl conjugation]]
[[Category: Z domain]]
[[Category: Z-dna]]
[[Category: Zinc]]