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| | <StructureSection load='2nrc' size='340' side='right'caption='[[2nrc]], [[Resolution|resolution]] 2.05Å' scene=''> | | <StructureSection load='2nrc' size='340' side='right'caption='[[2nrc]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2nrc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pig Pig]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NRC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NRC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2nrc]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NRC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NRC FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1m3e|1m3e]], [[1ooy|1ooy]], [[2nrb|2nrb]]</div></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]] 2.05Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">OXCT1, OXCT, SCOT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 PIG])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/3-oxoacid_CoA-transferase 3-oxoacid CoA-transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.8.3.5 2.8.3.5] </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=2nrc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nrc OCA], [https://pdbe.org/2nrc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nrc RCSB], [https://www.ebi.ac.uk/pdbsum/2nrc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nrc 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=2nrc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2nrc OCA], [https://pdbe.org/2nrc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2nrc RCSB], [https://www.ebi.ac.uk/pdbsum/2nrc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2nrc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SCOT1_PIG SCOT1_PIG]] Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate.
| + | [https://www.uniprot.org/uniprot/SCOT1_PIG SCOT1_PIG] Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 3-oxoacid CoA-transferase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Pig]] | + | [[Category: Sus scrofa]] |
| - | [[Category: Fraser, M E]] | + | [[Category: Fraser ME]] |
| - | [[Category: Tammam, S D]] | + | [[Category: Tammam SD]] |
| - | [[Category: Alpha/beta protein]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
SCOT1_PIG Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate.
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
Succinyl-CoA:3-ketoacid CoA transferase (SCOT) transfers CoA from succinyl-CoA to acetoacetate via a thioester intermediate with its active site glutamate residue, Glu 305. When CoA is linked to the enzyme, a cysteine residue can now be rapidly modified by 5,5'-dithiobis(2-nitrobenzoic acid), reflecting a conformational change of SCOT upon formation of the thioester. Since either Cys 28 or Cys 196 could be the target, each was mutated to Ser to distinguish between them. Like wild-type SCOT, the C196S mutant protein was modified rapidly in the presence of acyl-CoA substrates. In contrast, the C28S mutant protein was modified much more slowly under identical conditions, indicating that Cys 28 is the residue exposed on binding CoA. The specific activity of the C28S mutant protein was unexpectedly lower than that of wild-type SCOT. X-ray crystallography revealed that Ser adopts a different conformation than the native Cys. A chloride ion is bound to one of four active sites in the crystal structure of the C28S mutant protein, mimicking substrate, interacting with Lys 329, Asn 51, and Asn 52. On the basis of these results and the studies of the structurally similar CoA transferase from Escherichia coli, YdiF, bound to CoA, the conformational change in SCOT was deduced to be a domain rotation of 17 degrees coupled with movement of two loops: residues 321-329 that bury Cys 28 and interact with succinate or acetoacetate and residues 374-386 that interact with CoA. Modeling this conformational change has led to the proposal of a new mechanism for catalysis by SCOT.
Identification of the cysteine residue exposed by the conformational change in pig heart succinyl-CoA:3-ketoacid coenzyme A transferase on binding coenzyme A.,Tammam SD, Rochet JC, Fraser ME Biochemistry. 2007 Sep 25;46(38):10852-63. Epub 2007 Aug 24. PMID:17718512[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tammam SD, Rochet JC, Fraser ME. Identification of the cysteine residue exposed by the conformational change in pig heart succinyl-CoA:3-ketoacid coenzyme A transferase on binding coenzyme A. Biochemistry. 2007 Sep 25;46(38):10852-63. Epub 2007 Aug 24. PMID:17718512 doi:10.1021/bi700828h
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