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| | <StructureSection load='3qd9' size='340' side='right'caption='[[3qd9]], [[Resolution|resolution]] 3.30Å' scene=''> | | <StructureSection load='3qd9' size='340' side='right'caption='[[3qd9]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3qd9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_(trypanozoon)_brucei Trypanosoma (trypanozoon) brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QD9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QD9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3qd9]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QD9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QD9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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]] 3.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qcp|3qcp]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">QSOX, Tb927.6.1850 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5691 Trypanosoma (Trypanozoon) brucei])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thiol_oxidase Thiol oxidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.3.2 1.8.3.2] </span></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=3qd9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qd9 OCA], [https://pdbe.org/3qd9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qd9 RCSB], [https://www.ebi.ac.uk/pdbsum/3qd9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qd9 ProSAT]</span></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=3qd9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qd9 OCA], [https://pdbe.org/3qd9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qd9 RCSB], [https://www.ebi.ac.uk/pdbsum/3qd9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qd9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/Q585M6_TRYB2 Q585M6_TRYB2] |
| - | Protein stability, assembly, localization and regulation often depend on the formation of disulphide crosslinks between cysteine side chains. Enzymes known as sulphydryl oxidases catalyse de novo disulphide formation and initiate intra- and intermolecular dithiol/disulphide relays to deliver the disulphides to substrate proteins. Quiescin sulphydryl oxidase (QSOX) is a unique, multi-domain disulphide catalyst that is localized primarily to the Golgi apparatus and secreted fluids and has attracted attention owing to its overproduction in tumours. In addition to its physiological importance, QSOX is a mechanistically intriguing enzyme, encompassing functions typically carried out by a series of proteins in other disulphide-formation pathways. How disulphides are relayed through the multiple redox-active sites of QSOX and whether there is a functional benefit to concatenating these sites on a single polypeptide are open questions. Here we present the first crystal structure of an intact QSOX enzyme, derived from a trypanosome parasite. Notably, sequential sites in the disulphide relay were found more than 40 A apart in this structure, too far for direct disulphide transfer. To resolve this puzzle, we trapped and crystallized an intermediate in the disulphide hand-off, which showed a 165 degrees domain rotation relative to the original structure, bringing the two active sites within disulphide-bonding distance. The comparable structure of a mammalian QSOX enzyme, also presented here, shows further biochemical features that facilitate disulphide transfer in metazoan orthologues. Finally, we quantified the contribution of concatenation to QSOX activity, providing general lessons for the understanding of multi-domain enzymes and the design of new catalytic relays.
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| - | | + | |
| - | The dynamic disulphide relay of quiescin sulphydryl oxidase.,Alon A, Grossman I, Gat Y, Kodali VK, DiMaio F, Mehlman T, Haran G, Baker D, Thorpe C, Fass D Nature. 2012 Aug 16;488(7411):414-8. PMID:22801504<ref>PMID:22801504</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3qd9" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Sulfhydryl oxidase 3D structures|Sulfhydryl oxidase 3D structures]] | | *[[Sulfhydryl oxidase 3D structures|Sulfhydryl oxidase 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Thiol oxidase]] | + | [[Category: Trypanosoma brucei]] |
| - | [[Category: Alon, A]] | + | [[Category: Alon A]] |
| - | [[Category: Fass, D]] | + | [[Category: Fass D]] |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Erv fold]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Sulfhydryl oxidase]]
| + | |
| - | [[Category: Thioredoxin fold]]
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