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| | <StructureSection load='5exi' size='340' side='right'caption='[[5exi]], [[Resolution|resolution]] 2.28Å' scene=''> | | <StructureSection load='5exi' size='340' side='right'caption='[[5exi]], [[Resolution|resolution]] 2.28Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5exi]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EXI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EXI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5exi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EXI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DTV:(2S,3S)-1,4-DIMERCAPTOBUTANE-2,3-DIOL'>DTV</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</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]] 2.28Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5exj|5exj]], [[5exk|5exk]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTV:(2S,3S)-1,4-DIMERCAPTOBUTANE-2,3-DIOL'>DTV</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lipA, Rv2218, MTCY190.29 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=5exi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5exi OCA], [https://pdbe.org/5exi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5exi RCSB], [https://www.ebi.ac.uk/pdbsum/5exi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5exi 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/Lipoyl_synthase Lipoyl synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.8.1.8 2.8.1.8] </span></td></tr>
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| - | <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=5exi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5exi OCA], [http://pdbe.org/5exi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5exi RCSB], [http://www.ebi.ac.uk/pdbsum/5exi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5exi ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LIPA_MYCTU LIPA_MYCTU]] Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes, thereby converting the octanoylated domains into lipoylated derivatives. | + | [https://www.uniprot.org/uniprot/LIPA_MYCTU LIPA_MYCTU] Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes, thereby converting the octanoylated domains into lipoylated derivatives. |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Lipoyl synthase (LipA) catalyzes the insertion of two sulfur atoms at the unactivated C6 and C8 positions of a protein-bound octanoyl chain to produce the lipoyl cofactor. To activate its substrate for sulfur insertion, LipA uses a [4Fe-4S] cluster and S-adenosylmethionine (AdoMet) radical chemistry; the remainder of the reaction mechanism, especially the source of the sulfur, has been less clear. One controversial proposal involves the removal of sulfur from a second (auxiliary) [4Fe-4S] cluster on the enzyme, resulting in destruction of the cluster during each round of catalysis. Here, we present two high-resolution crystal structures of LipA from Mycobacterium tuberculosis: one in its resting state and one at an intermediate state during turnover. In the resting state, an auxiliary [4Fe-4S] cluster has an unusual serine ligation to one of the irons. After reaction with an octanoyllysine-containing 8-mer peptide substrate and 1 eq AdoMet, conditions that allow for the first sulfur insertion but not the second insertion, the serine ligand dissociates from the cluster, the iron ion is lost, and a sulfur atom that is still part of the cluster becomes covalently attached to C6 of the octanoyl substrate. This intermediate structure provides a clear picture of iron-sulfur cluster destruction in action, supporting the role of the auxiliary cluster as the sulfur source in the LipA reaction and describing a radical strategy for sulfur incorporation into completely unactivated substrates.
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| - | Crystallographic snapshots of sulfur insertion by lipoyl synthase.,McLaughlin MI, Lanz ND, Goldman PJ, Lee KH, Booker SJ, Drennan CL Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):9446-50. doi:, 10.1073/pnas.1602486113. Epub 2016 Aug 9. PMID:27506792<ref>PMID:27506792</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5exi" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lipoyl synthase]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Myctu]]
| + | [[Category: Booker SJ]] |
| - | [[Category: Booker, S J]] | + | [[Category: Drennan CL]] |
| - | [[Category: Drennan, C L]] | + | [[Category: Goldman PJ]] |
| - | [[Category: Goldman, P J]] | + | [[Category: Lanz ND]] |
| - | [[Category: Lanz, N D]] | + | [[Category: Lee K-H]] |
| - | [[Category: Lee, K H]] | + | [[Category: McLaughlin MI]] |
| - | [[Category: McLaughlin, M I]] | + | |
| - | [[Category: Adomet radical]]
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| - | [[Category: Auxiliary iron-sulfur cluster]]
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| - | [[Category: Radical sam]]
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| - | [[Category: Sulfur insertion]]
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| - | [[Category: Transferase]]
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