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| - | [[Image:1ikt.gif|left|200px]]<br /> | |
| - | <applet load="1ikt" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1ikt, resolution 1.75Å" /> | |
| - | '''LIGANDED STEROL CARRIER PROTEIN TYPE 2 (SCP-2) LIKE DOMAIN OF HUMAN MULTIFUNCTIONAL ENZYME TYPE 2 (MFE-2)'''<br /> | |
| | | | |
| - | ==Overview== | + | ==LIGANDED STEROL CARRIER PROTEIN TYPE 2 (SCP-2) LIKE DOMAIN OF HUMAN MULTIFUNCTIONAL ENZYME TYPE 2 (MFE-2)== |
| - | beta-Oxidation of amino acyl coenzyme A (acyl-CoA) species in mammalian, peroxisomes can occur via either multifunctional enzyme type 1 (MFE-1) or, type 2 (MFE-2), both of which catalyze the hydration of trans-2-enoyl-CoA, and the dehydrogenation of 3-hydroxyacyl-CoA, but with opposite chiral, specificity. MFE-2 has a modular organization of three domains. The, function of the C-terminal domain of the mammalian MFE-2, which shows, similarity with sterol carrier protein type 2 (SCP-2), is unclear. Here, the structure of the SCP-2-like domain comprising amino acid residues, 618-736 of human MFE-2 (d Delta h Delta SCP-2L) was solved at 1.75 A, resolution in complex with Triton X-100, an analog of a lipid molecule., This is the first reported structure of an MFE-2 domain. The d Delta h, Delta SCP-2L has an alpha/beta-fold consisting of five beta-strands and, five alpha-helices; the overall architecture resembles the rabbit and, human SCP-2 structures. However, the structure of d Delta h Delta SCP-2L, shows a hydrophobic tunnel that traverses the protein, which is occupied, by an ordered Triton X-100 molecule. The tunnel is large enough to, accommodate molecules such as straight-chain and branched-chain fatty, acyl-CoAs and bile acid intermediates. Large empty apolar cavities are, observed near the exit of the tunnel and between the helices C and D. In, addition, the C-terminal peroxisomal targeting signal is ordered in the, structure and solvent-exposed, which is not the case with unliganded, rabbit SCP-2, supporting the hypothesis of a ligand-assisted targeting, mechanism. | + | <StructureSection load='1ikt' size='340' side='right'caption='[[1ikt]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1ikt]] is a 1 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=1IKT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IKT 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]] 1.75Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=OXN:OXTOXYNOL-10'>OXN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1ikt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ikt OCA], [https://pdbe.org/1ikt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ikt RCSB], [https://www.ebi.ac.uk/pdbsum/1ikt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ikt ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/DHB4_HUMAN DHB4_HUMAN] Defects in HSD17B4 are a cause of D-bifunctional protein deficiency (DBPD) [MIM:[https://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:[https://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> |
| | + | == Function == |
| | + | [https://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> |
| | + | == 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/ik/1ikt_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=1ikt ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | beta-Oxidation of amino acyl coenzyme A (acyl-CoA) species in mammalian peroxisomes can occur via either multifunctional enzyme type 1 (MFE-1) or type 2 (MFE-2), both of which catalyze the hydration of trans-2-enoyl-CoA and the dehydrogenation of 3-hydroxyacyl-CoA, but with opposite chiral specificity. MFE-2 has a modular organization of three domains. The function of the C-terminal domain of the mammalian MFE-2, which shows similarity with sterol carrier protein type 2 (SCP-2), is unclear. Here, the structure of the SCP-2-like domain comprising amino acid residues 618-736 of human MFE-2 (d Delta h Delta SCP-2L) was solved at 1.75 A resolution in complex with Triton X-100, an analog of a lipid molecule. This is the first reported structure of an MFE-2 domain. The d Delta h Delta SCP-2L has an alpha/beta-fold consisting of five beta-strands and five alpha-helices; the overall architecture resembles the rabbit and human SCP-2 structures. However, the structure of d Delta h Delta SCP-2L shows a hydrophobic tunnel that traverses the protein, which is occupied by an ordered Triton X-100 molecule. The tunnel is large enough to accommodate molecules such as straight-chain and branched-chain fatty acyl-CoAs and bile acid intermediates. Large empty apolar cavities are observed near the exit of the tunnel and between the helices C and D. In addition, the C-terminal peroxisomal targeting signal is ordered in the structure and solvent-exposed, which is not the case with unliganded rabbit SCP-2, supporting the hypothesis of a ligand-assisted targeting mechanism. |
| | | | |
| - | ==Disease==
| + | Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution.,Haapalainen AM, van Aalten DM, Merilainen G, Jalonen JE, Pirila P, Wierenga RK, Hiltunen JK, Glumoff T J Mol Biol. 2001 Nov 9;313(5):1127-38. PMID:11700068<ref>PMID:11700068</ref> |
| - | Known disease associated with this structure: D-bifunctional protein deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601860 601860]]
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1IKT 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 SO4 and OXN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Estradiol_17-beta-dehydrogenase Estradiol 17-beta-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.62 1.1.1.62] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1IKT OCA].
| + | </div> |
| - | | + | <div class="pdbe-citations 1ikt" style="background-color:#fffaf0;"></div> |
| - | ==Reference== | + | == References == |
| - | Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution., Haapalainen AM, van Aalten DM, Merilainen G, Jalonen JE, Pirila P, Wierenga RK, Hiltunen JK, Glumoff T, J Mol Biol. 2001 Nov 9;313(5):1127-38. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11700068 11700068]
| + | <references/> |
| - | [[Category: Estradiol 17-beta-dehydrogenase]]
| + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Aalten, D.M.F.van.]]
| + | [[Category: Glumoff T]] |
| - | [[Category: Glumoff, T.]] | + | [[Category: Haapalainen AM]] |
| - | [[Category: Haapalainen, A.M.]] | + | [[Category: Van Aalten DMF]] |
| - | [[Category: OXN]] | + | |
| - | [[Category: SO4]]
| + | |
| - | [[Category: alfa-beta fold]]
| + | |
| - | [[Category: exposed peroxisomal targeting signal type 1 (pts1)]]
| + | |
| - | [[Category: hydrophobic tunnel]]
| + | |
| - | [[Category: protein-triton x-100 complex]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:30:58 2007''
| + | |
| Structural highlights
Disease
DHB4_HUMAN Defects in HSD17B4 are a cause of D-bifunctional protein deficiency (DBPD) [MIM:261515. DBPD is a disorder of peroxisomal fatty acid beta-oxidation.[1] [2] [3] Defects in HSD17B4 are the cause of Perrault syndrome (PRLTS1) [MIM: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.[4]
Function
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.[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
beta-Oxidation of amino acyl coenzyme A (acyl-CoA) species in mammalian peroxisomes can occur via either multifunctional enzyme type 1 (MFE-1) or type 2 (MFE-2), both of which catalyze the hydration of trans-2-enoyl-CoA and the dehydrogenation of 3-hydroxyacyl-CoA, but with opposite chiral specificity. MFE-2 has a modular organization of three domains. The function of the C-terminal domain of the mammalian MFE-2, which shows similarity with sterol carrier protein type 2 (SCP-2), is unclear. Here, the structure of the SCP-2-like domain comprising amino acid residues 618-736 of human MFE-2 (d Delta h Delta SCP-2L) was solved at 1.75 A resolution in complex with Triton X-100, an analog of a lipid molecule. This is the first reported structure of an MFE-2 domain. The d Delta h Delta SCP-2L has an alpha/beta-fold consisting of five beta-strands and five alpha-helices; the overall architecture resembles the rabbit and human SCP-2 structures. However, the structure of d Delta h Delta SCP-2L shows a hydrophobic tunnel that traverses the protein, which is occupied by an ordered Triton X-100 molecule. The tunnel is large enough to accommodate molecules such as straight-chain and branched-chain fatty acyl-CoAs and bile acid intermediates. Large empty apolar cavities are observed near the exit of the tunnel and between the helices C and D. In addition, the C-terminal peroxisomal targeting signal is ordered in the structure and solvent-exposed, which is not the case with unliganded rabbit SCP-2, supporting the hypothesis of a ligand-assisted targeting mechanism.
Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution.,Haapalainen AM, van Aalten DM, Merilainen G, Jalonen JE, Pirila P, Wierenga RK, Hiltunen JK, Glumoff T J Mol Biol. 2001 Nov 9;313(5):1127-38. PMID:11700068[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ van Grunsven EG, van Berkel E, Ijlst L, Vreken P, de Klerk JB, Adamski J, Lemonde H, Clayton PT, Cuebas DA, Wanders RJ. Peroxisomal D-hydroxyacyl-CoA dehydrogenase deficiency: resolution of the enzyme defect and its molecular basis in bifunctional protein deficiency. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2128-33. PMID:9482850
- ↑ van Grunsven EG, Mooijer PA, Aubourg P, Wanders RJ. Enoyl-CoA hydratase deficiency: identification of a new type of D-bifunctional protein deficiency. Hum Mol Genet. 1999 Aug;8(8):1509-16. PMID:10400999
- ↑ Nakano K, Zhang Z, Shimozawa N, Kondo N, Ishii N, Funatsuka M, Shirakawa S, Itoh M, Takashima S, Une M, Kana-aki RR, Mukai K, Osawa M, Suzuki Y. D-bifunctional protein deficiency with fetal ascites, polyhydramnios, and contractures of hands and toes. J Pediatr. 2001 Dec;139(6):865-7. PMID:11743515 doi:10.1067/mpd.2001.119170
- ↑ Pierce SB, Walsh T, Chisholm KM, Lee MK, Thornton AM, Fiumara A, Opitz JM, Levy-Lahad E, Klevit RE, King MC. Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome. Am J Hum Genet. 2010 Aug 13;87(2):282-8. doi: 10.1016/j.ajhg.2010.07.007. Epub, 2010 Jul 30. PMID:20673864 doi:10.1016/j.ajhg.2010.07.007
- ↑ Jiang LL, Miyazawa S, Souri M, Hashimoto T. Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein. J Biochem. 1997 Feb;121(2):364-9. PMID:9089413
- ↑ Jiang LL, Kobayashi A, Matsuura H, Fukushima H, Hashimoto T. Purification and properties of human D-3-hydroxyacyl-CoA dehydratase: medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase. J Biochem. 1996 Sep;120(3):624-32. PMID:8902629
- ↑ Haapalainen AM, van Aalten DM, Merilainen G, Jalonen JE, Pirila P, Wierenga RK, Hiltunen JK, Glumoff T. Crystal structure of the liganded SCP-2-like domain of human peroxisomal multifunctional enzyme type 2 at 1.75 A resolution. J Mol Biol. 2001 Nov 9;313(5):1127-38. PMID:11700068 doi:http://dx.doi.org/10.1006/jmbi.2001.5084
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