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| - | {{STRUCTURE_2zqr| PDB=2zqr | SCENE= }} | |
| - | ===Crystal structure of AUH without RNA=== | |
| - | {{ABSTRACT_PUBMED_18831052}} | |
| | | | |
| - | ==Disease== | + | ==Crystal structure of AUH without RNA== |
| - | [[http://www.uniprot.org/uniprot/AUHM_HUMAN AUHM_HUMAN]] Defects in AUH are the cause of 3-methylglutaconic aciduria type 1 (MGA1) [MIM:[http://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> | + | <StructureSection load='2zqr' size='340' side='right'caption='[[2zqr]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[2zqr]] 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=2ZQR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZQR 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]] 2.5Å</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=2zqr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zqr OCA], [https://pdbe.org/2zqr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zqr RCSB], [https://www.ebi.ac.uk/pdbsum/2zqr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zqr ProSAT], [https://www.topsan.org/Proteins/RSGI/2zqr 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/2zqr_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=2zqr 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. |
| | | | |
| - | ==Function==
| + | 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> |
| - | [[http://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>
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[2zqr]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZQR OCA].
| + | </div> |
| - | | + | <div class="pdbe-citations 2zqr" style="background-color:#fffaf0;"></div> |
| - | ==Reference==
| + | == References == |
| - | <ref group="xtra">PMID:018831052</ref><references group="xtra"/><references/> | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Methylglutaconyl-CoA hydratase]] | + | [[Category: Large Structures]] |
| - | [[Category: Kurimoto, K.]] | + | [[Category: Kurimoto K]] |
| - | [[Category: Kuwasako, K.]] | + | [[Category: Kuwasako K]] |
| - | [[Category: Muto, Y.]] | + | [[Category: Muto Y]] |
| - | [[Category: Nureki, O.]] | + | [[Category: Nureki O]] |
| - | [[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]]
| + | [[Category: Yokoyama S]] |
| - | [[Category: Yokoyama, S.]] | + | |
| - | [[Category: Beta spiral]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: National project on protein structural and functional analyse]]
| + | |
| - | [[Category: Nppsfa]]
| + | |
| - | [[Category: Riken structural genomics/proteomics initiative]]
| + | |
| - | [[Category: Rsgi]]
| + | |
| - | [[Category: Structural genomic]]
| + | |
| Structural highlights
Disease
AUHM_HUMAN Defects in AUH are the cause of 3-methylglutaconic aciduria type 1 (MGA1) [MIM: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).[1] [2]
Function
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.[3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ IJlst L, Loupatty FJ, Ruiter JP, Duran M, Lehnert W, Wanders RJ. 3-Methylglutaconic aciduria type I is caused by mutations in AUH. Am J Hum Genet. 2002 Dec;71(6):1463-6. Epub 2002 Nov 14. PMID:12434311 doi:S0002-9297(07)60868-4
- ↑ Ly TB, Peters V, Gibson KM, Liesert M, Buckel W, Wilcken B, Carpenter K, Ensenauer R, Hoffmann GF, Mack M, Zschocke J. Mutations in the AUH gene cause 3-methylglutaconic aciduria type I. Hum Mutat. 2003 Apr;21(4):401-7. PMID:12655555 doi:10.1002/humu.10202
- ↑ Nakagawa J, Waldner H, Meyer-Monard S, Hofsteenge J, Jeno P, Moroni C. AUH, a gene encoding an AU-specific RNA binding protein with intrinsic enoyl-CoA hydratase activity. Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2051-5. PMID:7892223
- ↑ IJlst L, Loupatty FJ, Ruiter JP, Duran M, Lehnert W, Wanders RJ. 3-Methylglutaconic aciduria type I is caused by mutations in AUH. Am J Hum Genet. 2002 Dec;71(6):1463-6. Epub 2002 Nov 14. PMID:12434311 doi:S0002-9297(07)60868-4
- ↑ Kurimoto K, Fukai S, Nureki O, Muto Y, Yokoyama S. Crystal structure of human AUH protein, a single-stranded RNA binding homolog of enoyl-CoA hydratase. Structure. 2001 Dec;9(12):1253-63. PMID:11738050
- ↑ Ly TB, Peters V, Gibson KM, Liesert M, Buckel W, Wilcken B, Carpenter K, Ensenauer R, Hoffmann GF, Mack M, Zschocke J. Mutations in the AUH gene cause 3-methylglutaconic aciduria type I. Hum Mutat. 2003 Apr;21(4):401-7. PMID:12655555 doi:10.1002/humu.10202
- ↑ Kurimoto K, Kuwasako K, Sandercock AM, Unzai S, Robinson CV, Muto Y, Yokoyama S. AU-rich RNA-binding induces changes in the quaternary structure of AUH. Proteins. 2009 May 1;75(2):360-72. PMID:18831052 doi:10.1002/prot.22246
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