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| | ==CRYSTAL STRUCTURE OF HUMAN AUH PROTEIN, AN RNA-BINDING HOMOLOGUE OF ENOYL-COA HYDRATASE== | | ==CRYSTAL STRUCTURE OF HUMAN AUH PROTEIN, AN RNA-BINDING HOMOLOGUE OF ENOYL-COA HYDRATASE== |
| - | <StructureSection load='1hzd' size='340' side='right' caption='[[1hzd]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='1hzd' size='340' side='right'caption='[[1hzd]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1hzd]] 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=1HZD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HZD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1hzd]] 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=1HZD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HZD FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1dub|1dub]], [[1dci|1dci]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AUH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=1hzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hzd OCA], [https://pdbe.org/1hzd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hzd RCSB], [https://www.ebi.ac.uk/pdbsum/1hzd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hzd ProSAT], [https://www.topsan.org/Proteins/RSGI/1hzd TOPSAN]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-CoA_hydratase Enoyl-CoA hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.17 4.2.1.17] </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=1hzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hzd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1hzd RCSB], [http://www.ebi.ac.uk/pdbsum/1hzd PDBsum], [http://www.topsan.org/Proteins/RSGI/1hzd TOPSAN]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[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> | + | [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 == | | == Function == |
| - | [[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> | + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hz/1hzd_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hz/1hzd_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </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/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </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=1hzd ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 1hzd" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Enoyl-CoA hydratase]] | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Fukai, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Kurimoto, K]] | + | [[Category: Fukai S]] |
| - | [[Category: Muto, Y]] | + | [[Category: Kurimoto K]] |
| - | [[Category: Nureki, O]] | + | [[Category: Muto Y]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Nureki O]] |
| - | [[Category: Yokoyama, S]] | + | [[Category: Yokoyama S]] |
| - | [[Category: Enoyl-coa hydratase]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Rna-binding protein]]
| + | |
| - | [[Category: Rsgi]]
| + | |
| 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
BACKGROUND: The AU binding homolog of enoyl-CoA hydratase (AUH) is a bifunctional protein that has two distinct activities: AUH binds to RNA and weakly catalyzes the hydration of 2-trans-enoyl-coenzyme A (enoyl-CoA). AUH has no sequence similarity with other known RNA binding proteins, but it has considerable sequence similarity with enoyl-CoA hydratase. A segment of AUH, named the R peptide, binds to RNA. However, the mechanism of the RNA binding activity of AUH remains to be elucidated. RESULTS: We determined the crystal structure of human AUH at 2.2 A resolution. AUH adopts the typical fold of the enoyl-CoA hydratase/isomerase superfamily and forms a hexamer as a dimer of trimers. Interestingly, the surface of the AUH hexamer is positively charged, in striking contrast to the negatively charged surfaces of the other members of the superfamily. Furthermore, wide clefts are uniquely formed between the two trimers of AUH and are highly positively charged with the Lys residues in alpha helix H1, which is located on the edge of the cleft and contains the majority of the R peptide. A mutational analysis showed that the lysine residues in alpha helix H1 are essential to the RNA binding activity of AUH. CONCLUSIONS: Alpha helix H1 exposes a row of Lys residues on the solvent-accessible surface. These characteristic Lys residues are named the "lysine comb." The distances between these Lys residues are similar to those between the RNA phosphate groups, suggesting that the lysine comb may continuously bind to a single-stranded RNA. The clefts between the trimers may provide spaces sufficient to accommodate the RNA bases.
Crystal structure of human AUH protein, a single-stranded RNA binding homolog of enoyl-CoA hydratase.,Kurimoto K, Fukai S, Nureki O, Muto Y, Yokoyama S Structure. 2001 Dec;9(12):1253-63. PMID:11738050[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, 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
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