LIPA_LEIBR
ID LIPA_LEIBR Reviewed; 379 AA.
AC A4H9Z3;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 1.
DT 03-AUG-2022, entry version 86.
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};
GN ORFNames=LbrM19_V2.0670, LbrM_19_0670;
OS Leishmania braziliensis.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania;
OC Leishmania braziliensis species complex.
OX NCBI_TaxID=5660;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MHOM/BR/75/M2904;
RX PubMed=17572675; DOI=10.1038/ng2053;
RA Peacock C.S., Seeger K., Harris D., Murphy L., Ruiz J.C., Quail M.A.,
RA Peters N., Adlem E., Tivey A., Aslett M., Kerhornou A., Ivens A.,
RA Fraser A., Rajandream M.-A., Carver T., Norbertczak H., Chillingworth T.,
RA Hance Z., Jagels K., Moule S., Ormond D., Rutter S., Sqaures R.,
RA Whitehead S., Rabbinowitsch E., Arrowsmith C., White B., Thurston S.,
RA Bringaud F., Baldauf S.L., Faulconbridge A., Jeffares D., Depledge D.P.,
RA Oyola S.O., Hilley J.D., Brito L.O., Tosi L.R.O., Barrell B., Cruz A.K.,
RA Mottram J.C., Smith D.F., Berriman M.;
RT "Comparative genomic analysis of three Leishmania species that cause
RT diverse human disease.";
RL Nat. Genet. 39:839-847(2007).
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 -!- MISCELLANEOUS: This protein may be expected to contain an N-terminal
CC transit peptide but none has been predicted. {ECO:0000255|HAMAP-
CC 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; FR798993; CAM38219.1; -; Genomic_DNA.
DR RefSeq; XP_001564163.2; XM_001564113.2.
DR AlphaFoldDB; A4H9Z3; -.
DR SMR; A4H9Z3; -.
DR STRING; 5660.A4H9Z3; -.
DR GeneID; 5414704; -.
DR KEGG; lbz:LBRM_19_0670; -.
DR VEuPathDB; TriTrypDB:LbrM.19.0670; -.
DR VEuPathDB; TriTrypDB:LBRM2903_190011300; -.
DR InParanoid; A4H9Z3; -.
DR OMA; PYCDIDF; -.
DR UniPathway; UPA00538; UER00593.
DR Proteomes; UP000007258; Chromosome 19.
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 SFLD; SFLDS00029; Radical_SAM; 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.
FT CHAIN 1..379
FT /note="Lipoyl synthase, mitochondrial"
FT /id="PRO_0000398236"
FT DOMAIN 109..331
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT BINDING 94
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 99
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 105
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 126
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 130
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 133
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 342
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 379 AA; 42320 MW; 6FEC94249B0FA50F CRC64;
MTDVDKKDPQ YKQIFLERFR KKLQSDKTGM SDLESFVELP EGITPVAASI GPIKRGSEPL
PPWLKLNVPK GMTHRPRFNR IRRSMREKKL STVCEEAKCP NIGECWGGGE DNGAATATIM
VMGSHCTRGC RFCSVLTSRR PPPLDPDEPE KVAAAVHEMG VDYIVMTMVD RDDLPDGGAS
HVSRCIRTIK EQNPELMLEA LVGDFHGDLK VVEQLAATPL SVYAHNIECV ERITPRVRDH
RATYKQSLQT LEHVTKWTNG KMLTKSSIML GLGEEEEEVR QTLRDLRTAG VSAVTLGQYL
QPSRTRLKVS RYAHPKEFEM WEKEAMSMGF LYCASGPMVR SSYRAGEYYI KNIVKQRENA
KGATTMEAVT AADAVAAGA
