View source for 2zqq


==Crystal structure of human AUH (3-methylglutaconyl-coa hydratase) mixed with (AUUU)24A RNA==
<StructureSection load='2zqq' size='340' side='right'caption='[[2zqq]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2zqq]] is a 6 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=2ZQQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZQQ 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]] 2.2&#8491;</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=2zqq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zqq OCA], [https://pdbe.org/2zqq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zqq RCSB], [https://www.ebi.ac.uk/pdbsum/2zqq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zqq ProSAT], [https://www.topsan.org/Proteins/RSGI/2zqq TOPSAN]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/AUHM_HUMAN AUHM_HUMAN] Defects in AUH are the cause of 3-methylglutaconic aciduria type 1 (MGA1) [MIM:[https://omim.org/entry/250950 250950]. MGA1 is an inborn error of leucine metabolism. It leads to an autosomal recessive syndrome with variable clinical phenotype, ranging from delayed speech development to severe psychomotor retardation, coma, failure to thrive, metabolic acidosis and dystonia. MGA1 can be distinguished from other forms of MGA by the pattern of metabolite excretion: 3-methylglutaconic acid levels are higher than those detected in other forms, whereas methylglutaric acid levels are usually only slightly elevated, and there is a high level of 3-hydroxyisovaleric acid excretion (not present in other MGA forms).<ref>PMID:12434311</ref> <ref>PMID:12655555</ref> 
== Function ==
[https://www.uniprot.org/uniprot/AUHM_HUMAN AUHM_HUMAN] Catalyzes the conversion of 3-methylglutaconyl-CoA to 3-hydroxy-3-methylglutaryl-CoA. Has very low enoyl-CoA hydratase activity. Was originally identified as RNA-binding protein that binds in vitro to clustered 5'-AUUUA-3' motifs.<ref>PMID:7892223</ref> <ref>PMID:12434311</ref> <ref>PMID:11738050</ref> <ref>PMID:12655555</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/zq/2zqq_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=2zqq ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The human AU RNA binding protein/enoyl-Coenzyme A hydratase (AUH) is a 3-hydroxy-3-methylglutaconyl-CoA dehydratase in the leucine degradation pathway. It also possesses an RNA-binding activity to AUUU repeats, which involves no known conserved RNA-binding domains and is seemingly unrelated to the enzymatic activity. In this study, we performed mass spectrometric analyses to elucidate the oligomeric states of AUH in the presence and absence of RNA. With a short RNA (AUUU) or without RNA, AUH mainly exists as a trimer in solution. On the other hand, the AUH trimer dimerizes upon binding to one molecule of a long RNA containing 24 repeats of the AUUU motif, (AUUU)(24)A. AUH was crystallized with the long RNA. Although the RNA was disordered in the crystalline lattice, the AUH structure was determined as an asymmetric dimer of trimers with a kink in the alignment of the trimer axes, resulting in the formation of two clefts with significantly different sizes.

AU-rich RNA-binding induces changes in the quaternary structure of AUH.,Kurimoto K, Kuwasako K, Sandercock AM, Unzai S, Robinson CV, Muto Y, Yokoyama S Proteins. 2009 May 1;75(2):360-72. PMID:18831052<ref>PMID:18831052</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2zqq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kurimoto K]]
[[Category: Kuwasako K]]
[[Category: Muto Y]]
[[Category: Nureki O]]
[[Category: Yokoyama S]]