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New page: left|200px<br /> <applet load="1zy7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zy7, resolution 1.70Å" /> '''Crystal structure o...
 
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[[Image:1zy7.gif|left|200px]]<br />
<applet load="1zy7" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1zy7, resolution 1.70&Aring;" />
'''Crystal structure of the catalytic domain of an adenosine deaminase that acts on RNA (hADAR2) bound to inositol hexakisphosphate (IHP)'''<br />


==Overview==
==Crystal structure of the catalytic domain of an adenosine deaminase that acts on RNA (hADAR2) bound to inositol hexakisphosphate (IHP)==
We report the crystal structure of the catalytic domain of human ADAR2, an, RNA editing enzyme, at 1.7 angstrom resolution. The structure reveals a, zinc ion in the active site and suggests how the substrate adenosine is, recognized. Unexpectedly, inositol hexakisphosphate (IP6) is buried within, the enzyme core, contributing to the protein fold. Although there are no, reports that adenosine deaminases that act on RNA (ADARs) require a, cofactor, we show that IP6 is required for activity. Amino acids that, coordinate IP6 in the crystal structure are conserved in some adenosine, deaminases that act on transfer RNA (tRNA) (ADATs), related enzymes that, edit tRNA. Indeed, IP6 is also essential for in vivo and in vitro, deamination of adenosine 37 of tRNAala by ADAT1.
<StructureSection load='1zy7' size='340' side='right'caption='[[1zy7]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1zy7]] is a 2 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=1ZY7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZY7 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=1zy7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zy7 OCA], [https://pdbe.org/1zy7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zy7 RCSB], [https://www.ebi.ac.uk/pdbsum/1zy7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zy7 ProSAT]</span></td></tr>
</table>
== Function ==
[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>
== 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/zy/1zy7_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=1zy7 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1ZY7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, SO4 and IHP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZY7 OCA].
*[[Adenosine deaminase 3D structures|Adenosine deaminase 3D structures]]
 
== References ==
==Reference==
<references/>
Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing., Macbeth MR, Schubert HL, Vandemark AP, Lingam AT, Hill CP, Bass BL, Science. 2005 Sep 2;309(5740):1534-9. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16141067 16141067]
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Bass, B.L.]]
[[Category: Bass BL]]
[[Category: Hill, C.P.]]
[[Category: Hill CP]]
[[Category: Lingam, A.T.]]
[[Category: Lingam AT]]
[[Category: Macbeth, M.R.]]
[[Category: Macbeth MR]]
[[Category: Schubert, H.L.]]
[[Category: Schubert HL]]
[[Category: Vandemark, A.P.]]
[[Category: Vandemark AP]]
[[Category: IHP]]
[[Category: SO4]]
[[Category: ZN]]
[[Category: alpha/beta deaminase motif]]
[[Category: ionsitol hexakisphosphate]]
[[Category: zinc coordination]]
 
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