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| | ==Crystal structure of the zebrafish peroxisomal SCP2-thiolase (type-1)== | | ==Crystal structure of the zebrafish peroxisomal SCP2-thiolase (type-1)== |
| - | <StructureSection load='6hrv' size='340' side='right' caption='[[6hrv]], [[Resolution|resolution]] 1.95Å' scene=''> | + | <StructureSection load='6hrv' size='340' side='right'caption='[[6hrv]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6hrv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HRV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HRV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6hrv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HRV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HRV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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]] 1.95Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">scp2a, scp2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7955 Brachidanio rerio])</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=6hrv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hrv OCA], [https://pdbe.org/6hrv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hrv RCSB], [https://www.ebi.ac.uk/pdbsum/6hrv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hrv ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Propanoyl-CoA_C-acyltransferase Propanoyl-CoA C-acyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.176 2.3.1.176] </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=6hrv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hrv OCA], [http://pdbe.org/6hrv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hrv RCSB], [http://www.ebi.ac.uk/pdbsum/6hrv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hrv ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q6P4V5_DANRE Q6P4V5_DANRE] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brachidanio rerio]] | + | [[Category: Danio rerio]] |
| - | [[Category: Propanoyl-CoA C-acyltransferase]] | + | [[Category: Large Structures]] |
| - | [[Category: Kiema, T R]] | + | [[Category: Kiema TR]] |
| - | [[Category: Thapa, C J]] | + | [[Category: Thapa CJ]] |
| - | [[Category: Wierenga, R K]] | + | [[Category: Wierenga RK]] |
| - | [[Category: Bile acid biosynthesis]]
| + | |
| - | [[Category: Fatty acid metabolism]]
| + | |
| - | [[Category: Peroxisomal beta-oxidation]]
| + | |
| - | [[Category: Thiolytic cleavage]]
| + | |
| - | [[Category: Transferase]]
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| Structural highlights
Function
Q6P4V5_DANRE
Publication Abstract from PubMed
The SCP2-thiolase (type-1) functions in the vertebrate peroxisomal, bile acid synthesis pathway, converting 24-keto-THC-CoA and CoA into choloyl-CoA and propionyl-CoA. This conversion concerns the beta-oxidation chain shortening of the steroid fatty acyl moiety of 24-keto-THC-CoA. This class of dimeric thiolases has previously been poorly characterized. High resolution crystal structures of the zebrafish SCP2-thiolase (type-1) now reveal an open catalytic site, shaped by residues of both subunits. The structure of its non-dimerised monomeric form has also been captured in the obtained crystals. Four loops at the dimer interface adopt very different conformations in the monomeric form. These loops also shape the active site and their structural changes explain why a competent active site is not present in the monomeric form. Native mass spectrometry studies confirm that the zebrafish SCP2-thiolase (type-1) as well as its human homologue are weak transient dimers in solution. The crystallographic binding studies reveal the mode of binding of CoA and octanoyl-CoA in the active site, highlighting the conserved geometry of the nucleophilic cysteine, the catalytic acid/base cysteine and the two oxyanion holes. The dimer interface of SCP2-thiolase (type-1) is equally extensive as in other thiolase dimers, however it is more polar than any of the corresponding interfaces, which correlates with the notion that the enzyme forms a weak transient dimer. The structure comparison of the monomeric and dimeric forms suggests functional relevance of this property. These comparisons provide also insight into the structural rearrangements that occur when the folded inactive monomers assemble into the mature dimer.
The peroxisomal zebrafish SCP2-thiolase (type-1) is a weak transient dimer as revealed by crystal structures and native mass spectrometry.,Kiema TR, Thapa CJ, Laitaoja M, Schmitz W, Maksimainen MM, Fukao T, Rouvinen J, Janis J, Wierenga RK Biochem J. 2018 Dec 20. pii: BCJ20180788. doi: 10.1042/BCJ20180788. PMID:30573650[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kiema TR, Thapa CJ, Laitaoja M, Schmitz W, Maksimainen MM, Fukao T, Rouvinen J, Janis J, Wierenga RK. The peroxisomal zebrafish SCP2-thiolase (type-1) is a weak transient dimer as revealed by crystal structures and native mass spectrometry. Biochem J. 2018 Dec 20. pii: BCJ20180788. doi: 10.1042/BCJ20180788. PMID:30573650 doi:http://dx.doi.org/10.1042/BCJ20180788
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