LIPA_LACTC
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 03-AUG-2022, entry version 73.
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 = (R)-
CC N(6)-dihydrolipoyl-L-lysyl-[protein] + 2 5'-deoxyadenosine + [[Fe-S]
CC cluster scaffold protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 L-
CC methionine + 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 EnsemblFungi; CAR22687; CAR22687; KLTH0D09548g.
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; 610833at2759; -.
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:0102552; F:lipoyl synthase activity (acting on glycine-cleavage complex H protein; IEA:UniProtKB-EC.
DR GO; GO:0102553; F:lipoyl synthase activity (acting on pyruvate dehydrogenase E2 protein); IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009249; P:protein lipoylation; IEA:UniProtKB-UniRule.
DR Gene3D; 3.20.20.70; -; 1.
DR HAMAP; MF_00206; Lipoyl_synth; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR006638; Elp3/MiaB/NifB.
DR InterPro; IPR031691; LIAS_N.
DR InterPro; IPR003698; Lipoyl_synth.
DR InterPro; IPR007197; rSAM.
DR PANTHER; PTHR10949; PTHR10949; 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 SMART; SM00729; Elp3; 1.
DR TIGRFAMs; TIGR00510; lipA; 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
