1s9c

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{{STRUCTURE_1s9c| PDB=1s9c | SCENE= }}
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==Crystal structure analysis of the 2-enoyl-CoA hydratase 2 domain of human peroxisomal multifunctional enzyme type 2==
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===Crystal structure analysis of the 2-enoyl-CoA hydratase 2 domain of human peroxisomal multifunctional enzyme type 2===
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<StructureSection load='1s9c' size='340' side='right' caption='[[1s9c]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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{{ABSTRACT_PUBMED_15644212}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1s9c]] is a 12 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=1S9C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1S9C FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1pn2|1pn2]], [[1pn4|1pn4]]</td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSD17B4, EDH17B4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1s9c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s9c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1s9c RCSB], [http://www.ebi.ac.uk/pdbsum/1s9c PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/DHB4_HUMAN DHB4_HUMAN]] Defects in HSD17B4 are a cause of D-bifunctional protein deficiency (DBPD) [MIM:[http://omim.org/entry/261515 261515]]. DBPD is a disorder of peroxisomal fatty acid beta-oxidation.<ref>PMID:9482850</ref> <ref>PMID:10400999</ref> <ref>PMID:11743515</ref> Defects in HSD17B4 are the cause of Perrault syndrome (PRLTS1) [MIM:[http://omim.org/entry/233400 233400]]. A sex-influenced disorder characterized by sensorineural deafness in both males and females and ovarian dysgenesis in females. Some patients also have neurologic manifestations, including mild mental retardation and cerebellar and peripheral nervous system involvement.<ref>PMID:20673864</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/DHB4_HUMAN DHB4_HUMAN]] Bifunctional enzyme acting on the peroxisomal beta-oxidation pathway for fatty acids. Catalyzes the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids.<ref>PMID:9089413</ref> <ref>PMID:8902629</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/s9/1s9c_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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2-Enoyl-CoA hydratase 2 is the middle part of the mammalian peroxisomal multifunctional enzyme type 2 (MFE-2), which is known to be important in the beta-oxidation of very-long-chain and alpha-methyl-branched fatty acids as well as in the synthesis of bile acids. Here, we present the crystal structure of the hydratase 2 from the human MFE-2 to 3A resolution. The three-dimensional structure resembles the recently solved crystal structure of hydratase 2 from the yeast, Candida tropicalis, MFE-2 having a two-domain subunit structure with a C-domain complete hot-dog fold housing the active site, and an N-domain incomplete hot-dog fold housing the cavity for the aliphatic acyl part of the substrate molecule. The ability of human hydratase 2 to utilize such bulky compounds which are not physiological substrates for the fungal ortholog, e.g. CoA esters of C26 fatty acids, pristanic acid and di/trihydroxycholestanoic acids, is explained by a large hydrophobic cavity formed upon the movements of the extremely mobile loops I-III in the N-domain. In the unliganded form of human hydratase 2, however, the loop I blocks the entrance of fatty enoyl-CoAs with chain-length &gt;C8. Therefore, we expect that upon binding of substrates bulkier than C8, the loop I gives way, contemporaneously causing a secondary effect in the CoA-binding pocket and/or active site required for efficient hydration reaction. This structural feature would explain the inactivity of human hydratase 2 towards short-chain substrates. The solved structure is also used as a tool for analyzing the various inactivating mutations, identified among others in MFE-2-deficient patients. Since hydratase 2 is the last functional unit of mammalian MFE-2 whose structure has been solved, the organization of the functional units in the biologically active full-length enzyme is also discussed.
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==Disease==
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Crystal structure of 2-enoyl-CoA hydratase 2 from human peroxisomal multifunctional enzyme type 2.,Koski KM, Haapalainen AM, Hiltunen JK, Glumoff T J Mol Biol. 2005 Feb 4;345(5):1157-69. Epub 2004 Dec 10. PMID:15644212<ref>PMID:15644212</ref>
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[[http://www.uniprot.org/uniprot/DHB4_HUMAN DHB4_HUMAN]] Defects in HSD17B4 are a cause of D-bifunctional protein deficiency (DBPD) [MIM:[http://omim.org/entry/261515 261515]]. DBPD is a disorder of peroxisomal fatty acid beta-oxidation.<ref>PMID:9482850</ref><ref>PMID:10400999</ref><ref>PMID:11743515</ref> Defects in HSD17B4 are the cause of Perrault syndrome (PRLTS1) [MIM:[http://omim.org/entry/233400 233400]]. A sex-influenced disorder characterized by sensorineural deafness in both males and females and ovarian dysgenesis in females. Some patients also have neurologic manifestations, including mild mental retardation and cerebellar and peripheral nervous system involvement.<ref>PMID:20673864</ref>
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/DHB4_HUMAN DHB4_HUMAN]] Bifunctional enzyme acting on the peroxisomal beta-oxidation pathway for fatty acids. Catalyzes the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids.<ref>PMID:9089413</ref><ref>PMID:8902629</ref>
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</div>
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==About this Structure==
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[[1s9c]] is a 12 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=1S9C OCA].
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==See Also==
==See Also==
*[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]]
*[[Hydroxysteroid dehydrogenase|Hydroxysteroid dehydrogenase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:015644212</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Glumoff, T.]]
[[Category: Glumoff, T.]]

Revision as of 17:14, 29 September 2014

Crystal structure analysis of the 2-enoyl-CoA hydratase 2 domain of human peroxisomal multifunctional enzyme type 2

1s9c, resolution 3.00Å

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