ID LIPA_FRATF Reviewed; 327 AA. AC A7NBV0; DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot. DT 02-OCT-2007, sequence version 1. DT 27-MAR-2024, entry version 91. DE RecName: Full=Lipoyl synthase {ECO:0000255|HAMAP-Rule:MF_00206}; DE EC=2.8.1.8 {ECO:0000255|HAMAP-Rule:MF_00206}; DE AltName: Full=Lip-syn {ECO:0000255|HAMAP-Rule:MF_00206}; DE Short=LS {ECO:0000255|HAMAP-Rule:MF_00206}; DE AltName: Full=Lipoate synthase {ECO:0000255|HAMAP-Rule:MF_00206}; DE AltName: Full=Lipoic acid synthase {ECO:0000255|HAMAP-Rule:MF_00206}; DE AltName: Full=Sulfur insertion protein LipA {ECO:0000255|HAMAP-Rule:MF_00206}; GN Name=lipA {ECO:0000255|HAMAP-Rule:MF_00206}; GN OrderedLocusNames=FTA_0977; OS Francisella tularensis subsp. holarctica (strain FTNF002-00 / FTA). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Thiotrichales; OC Francisellaceae; Francisella. OX NCBI_TaxID=458234; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=FTNF002-00 / FTA; RX PubMed=19756146; DOI=10.1371/journal.pone.0007041; RA Barabote R.D., Xie G., Brettin T.S., Hinrichs S.H., Fey P.D., Jay J.J., RA Engle J.L., Godbole S.D., Noronha J.M., Scheuermann R.H., Zhou L.W., RA Lion C., Dempsey M.P.; RT "Complete genome sequence of Francisella tularensis subspecies holarctica RT FTNF002-00."; RL PLoS ONE 4:E7041-E7041(2009). CC -!- FUNCTION: Catalyzes the radical-mediated insertion of two sulfur atoms CC into the C-6 and C-8 positions of the octanoyl moiety bound to the CC lipoyl domains of lipoate-dependent enzymes, thereby converting the CC octanoylated domains into lipoylated derivatives. {ECO:0000255|HAMAP- CC Rule:MF_00206}. CC -!- CATALYTIC ACTIVITY: CC Reaction=[[Fe-S] cluster scaffold protein carrying a second [4Fe- CC 4S](2+) cluster] + 4 H(+) + N(6)-octanoyl-L-lysyl-[protein] + 2 CC oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine = 2 5'- CC deoxyadenosine + [[Fe-S] cluster scaffold protein] + 4 Fe(3+) + 2 CC hydrogen sulfide + 2 L-methionine + N(6)-[(R)-dihydrolipoyl]-L-lysyl- CC [protein] + 2 reduced [2Fe-2S]-[ferredoxin]; Xref=Rhea:RHEA:16585, CC Rhea:RHEA-COMP:9928, Rhea:RHEA-COMP:10000, Rhea:RHEA-COMP:10001, CC Rhea:RHEA-COMP:10475, Rhea:RHEA-COMP:14568, Rhea:RHEA-COMP:14569, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17319, ChEBI:CHEBI:29034, CC ChEBI:CHEBI:29919, ChEBI:CHEBI:33722, ChEBI:CHEBI:33737, CC ChEBI:CHEBI:33738, ChEBI:CHEBI:57844, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:78809, ChEBI:CHEBI:83100; EC=2.8.1.8; CC Evidence={ECO:0000255|HAMAP-Rule:MF_00206}; CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; CC Evidence={ECO:0000255|HAMAP-Rule:MF_00206}; CC Note=Binds 2 [4Fe-4S] clusters per subunit. One cluster is coordinated CC with 3 cysteines and an exchangeable S-adenosyl-L-methionine. CC {ECO:0000255|HAMAP-Rule:MF_00206}; CC -!- PATHWAY: Protein modification; protein lipoylation via endogenous CC pathway; protein N(6)-(lipoyl)lysine from octanoyl-[acyl-carrier- CC protein]: step 2/2. {ECO:0000255|HAMAP-Rule:MF_00206}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00206}. CC -!- SIMILARITY: Belongs to the radical SAM superfamily. Lipoyl synthase CC family. {ECO:0000255|HAMAP-Rule:MF_00206}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CP000803; ABU61453.1; -; Genomic_DNA. DR RefSeq; WP_003015696.1; NC_009749.1. DR AlphaFoldDB; A7NBV0; -. DR SMR; A7NBV0; -. DR KEGG; fta:FTA_0977; -. DR HOGENOM; CLU_033144_2_0_6; -. DR UniPathway; UPA00538; UER00593. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-UniRule. DR GO; GO:0016992; F:lipoate synthase activity; IEA:UniProtKB-UniRule. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR Gene3D; 3.20.20.70; Aldolase class I; 1. DR HAMAP; MF_00206; Lipoyl_synth; 1. DR InterPro; IPR013785; Aldolase_TIM. DR InterPro; IPR006638; Elp3/MiaA/NifB-like_rSAM. DR InterPro; IPR031691; LIAS_N. DR InterPro; IPR003698; Lipoyl_synth. DR InterPro; IPR007197; rSAM. DR NCBIfam; TIGR00510; lipA; 1. DR PANTHER; PTHR10949; LIPOYL SYNTHASE; 1. DR PANTHER; PTHR10949:SF0; LIPOYL SYNTHASE, MITOCHONDRIAL; 1. DR Pfam; PF16881; LIAS_N; 1. DR Pfam; PF04055; Radical_SAM; 1. DR PIRSF; PIRSF005963; Lipoyl_synth; 1. DR SFLD; SFLDF00271; lipoyl_synthase; 1. DR SFLD; SFLDG01058; lipoyl_synthase_like; 1. DR SMART; SM00729; Elp3; 1. DR SUPFAM; SSF102114; Radical SAM enzymes; 1. DR PROSITE; PS51918; RADICAL_SAM; 1. PE 3: Inferred from homology; KW 4Fe-4S; Cytoplasm; Iron; Iron-sulfur; Metal-binding; KW S-adenosyl-L-methionine; Transferase. FT CHAIN 1..327 FT /note="Lipoyl synthase" FT /id="PRO_0000325250" FT DOMAIN 83..302 FT /note="Radical SAM core" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266" FT BINDING 72 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00206" FT BINDING 77 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00206" FT BINDING 83 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00206" FT BINDING 98 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /ligand_note="4Fe-4S-S-AdoMet" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00206" FT BINDING 102 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /ligand_note="4Fe-4S-S-AdoMet" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00206" FT BINDING 105 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /ligand_note="4Fe-4S-S-AdoMet" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00206" FT BINDING 313 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00206" SQ SEQUENCE 327 AA; 36866 MW; 2A50F0D58A855C89 CRC64; MKEISGIKVK VESGSKYTTD HGFYAVKDGI RNKKENAVHV RKPDWLKVQK QDSKEYLKVK SITKKHKLST VCEEARCPNI NECWSHGTAT IMLMGSVCTR ACKFCSVDTG NPKGWLDKDE PMNAAESVKL MGLEYVVLTS VDRDDLEDGG AGHYAATITA IKNLDENIKV EALTPDFAGI NENIDKIINT KVDVIAQNIE TVERLTHPVR DPRAGYWQTL NFLKYVKQKS PNVLTKTSIM VGLGETDEEI YKTMDDARSV GVDIITLGQY MQPTKHHLSV ERFVTPQQFE EYRKVGLEKG FLEVASGPMV RSSYRADRVF KRNNLDL //