ID   LIPA_LACTC              Reviewed;         371 AA.
AC   C5DGZ5;
DT   05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT   28-JUL-2009, sequence version 1.
DT   24-JAN-2024, entry version 79.
DE   RecName: Full=Lipoyl synthase, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03123};
DE            EC=2.8.1.8 {ECO:0000255|HAMAP-Rule:MF_03123};
DE   AltName: Full=Lipoate synthase {ECO:0000255|HAMAP-Rule:MF_03123};
DE            Short=LS {ECO:0000255|HAMAP-Rule:MF_03123};
DE            Short=Lip-syn {ECO:0000255|HAMAP-Rule:MF_03123};
DE   AltName: Full=Lipoic acid synthase {ECO:0000255|HAMAP-Rule:MF_03123};
DE   Flags: Precursor;
GN   OrderedLocusNames=KLTH0D09548g;
OS   Lachancea thermotolerans (strain ATCC 56472 / CBS 6340 / NRRL Y-8284)
OS   (Yeast) (Kluyveromyces thermotolerans).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Lachancea.
OX   NCBI_TaxID=559295;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 56472 / CBS 6340 / NRRL Y-8284;
RX   PubMed=19525356; DOI=10.1101/gr.091546.109;
RG   The Genolevures Consortium;
RA   Souciet J.-L., Dujon B., Gaillardin C., Johnston M., Baret P.V.,
RA   Cliften P., Sherman D.J., Weissenbach J., Westhof E., Wincker P., Jubin C.,
RA   Poulain J., Barbe V., Segurens B., Artiguenave F., Anthouard V.,
RA   Vacherie B., Val M.-E., Fulton R.S., Minx P., Wilson R., Durrens P.,
RA   Jean G., Marck C., Martin T., Nikolski M., Rolland T., Seret M.-L.,
RA   Casaregola S., Despons L., Fairhead C., Fischer G., Lafontaine I., Leh V.,
RA   Lemaire M., de Montigny J., Neuveglise C., Thierry A., Blanc-Lenfle I.,
RA   Bleykasten C., Diffels J., Fritsch E., Frangeul L., Goeffon A.,
RA   Jauniaux N., Kachouri-Lafond R., Payen C., Potier S., Pribylova L.,
RA   Ozanne C., Richard G.-F., Sacerdot C., Straub M.-L., Talla E.;
RT   "Comparative genomics of protoploid Saccharomycetaceae.";
RL   Genome Res. 19:1696-1709(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_03123}.
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_03123};
CC   -!- COFACTOR:
CC       Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_03123};
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_03123};
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_03123}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03123}.
CC   -!- SIMILARITY: Belongs to the radical SAM superfamily. Lipoyl synthase
CC       family. {ECO:0000255|HAMAP-Rule:MF_03123}.
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DR   EMBL; CU928168; CAR22687.1; -; Genomic_DNA.
DR   RefSeq; XP_002553125.1; XM_002553079.1.
DR   AlphaFoldDB; C5DGZ5; -.
DR   SMR; C5DGZ5; -.
DR   STRING; 559295.C5DGZ5; -.
DR   GeneID; 8295363; -.
DR   KEGG; lth:KLTH0D09548g; -.
DR   eggNOG; KOG2672; Eukaryota.
DR   HOGENOM; CLU_033144_2_0_1; -.
DR   InParanoid; C5DGZ5; -.
DR   OMA; PYCDIDF; -.
DR   OrthoDB; 575at2759; -.
DR   UniPathway; UPA00538; UER00593.
DR   Proteomes; UP000002036; Chromosome D.
DR   GO; GO:0005739; C:mitochondrion; 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   CDD; cd01335; Radical_SAM; 1.
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; Iron; Iron-sulfur; Metal-binding; Mitochondrion;
KW   Reference proteome; S-adenosyl-L-methionine; Transferase; Transit peptide.
FT   TRANSIT         1..24
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03123"
FT   CHAIN           25..371
FT                   /note="Lipoyl synthase, mitochondrial"
FT                   /id="PRO_0000398270"
FT   DOMAIN          121..342
FT                   /note="Radical SAM core"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT   REGION          20..42
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         107
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03123"
FT   BINDING         112
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03123"
FT   BINDING         118
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03123"
FT   BINDING         138
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_03123"
FT   BINDING         142
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_03123"
FT   BINDING         145
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_03123"
FT   BINDING         353
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03123"
SQ   SEQUENCE   371 AA;  41451 MW;  54736E8D8C575ECB CRC64;
     MLSRFKCSRL QLQKRAISVT KATTTTASQP KRRRTTTFSD ALNKGPSFED FVSGKAAKFT
     LDPLQQARSN IEEAKRLPRW LKVPIPKGTN YHKLKKDVRE LKLSTVCEEA KCPNISECWG
     GGDSSKATAT IMLLGDTCTR GCRFCSVKTN RAPSKPDPAE PENTAEAISR WGLGYVVLTT
     VDRDDLADGG AHHLAETVCR IKQKAPKTLV ETLSGDFRGD LEMVKVMAQS GLDVYAHNLE
     TVKDLTPHVR DRRATYEQSL SVLNQAKKTV PTLITKTSLM LGLGETDEQV LQTLQDLRAI
     GCDVVTFGQY MRPTKRHMKV VEYVKPEKFD YWRDKALELG FLYCASGPLV RSSYKAGEAF
     IENVLRKRAN N
//