ID   LIPA_PLAKH              Reviewed;         442 AA.
AC   B3L8F2;
DT   05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT   02-SEP-2008, sequence version 1.
DT   24-JAN-2024, entry version 82.
DE   RecName: Full=Lipoyl synthase, apicoplast {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   Name=lipA {ECO:0000255|HAMAP-Rule:MF_03123}; ORFNames=PKH_120980;
OS   Plasmodium knowlesi (strain H).
OC   Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC   Plasmodiidae; Plasmodium; Plasmodium (Plasmodium).
OX   NCBI_TaxID=5851;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=H;
RX   PubMed=18843368; DOI=10.1038/nature07306;
RA   Pain A., Boehme U., Berry A.E., Mungall K., Finn R.D., Jackson A.P.,
RA   Mourier T., Mistry J., Pasini E.M., Aslett M.A., Balasubrammaniam S.,
RA   Borgwardt K., Brooks K., Carret C., Carver T.J., Cherevach I.,
RA   Chillingworth T., Clark T.G., Galinski M.R., Hall N., Harper D., Harris D.,
RA   Hauser H., Ivens A., Janssen C.S., Keane T., Larke N., Lapp S., Marti M.,
RA   Moule S., Meyer I.M., Ormond D., Peters N., Sanders M., Sanders S.,
RA   Sargeant T.J., Simmonds M., Smith F., Squares R., Thurston S., Tivey A.R.,
RA   Walker D., White B., Zuiderwijk E., Churcher C., Quail M.A., Cowman A.F.,
RA   Turner C.M.R., Rajandream M.A., Kocken C.H.M., Thomas A.W., Newbold C.I.,
RA   Barrell B.G., Berriman M.;
RT   "The genome of the simian and human malaria parasite Plasmodium knowlesi.";
RL   Nature 455:799-803(2008).
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: Plastid, apicoplast {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; AM910994; CAQ41175.1; -; Genomic_DNA.
DR   RefSeq; XP_002259908.1; XM_002259872.1.
DR   AlphaFoldDB; B3L8F2; -.
DR   SMR; B3L8F2; -.
DR   STRING; 5851.B3L8F2; -.
DR   EnsemblProtists; CAQ41175; CAQ41175; PKH_120980.
DR   GeneID; 7322246; -.
DR   KEGG; pkn:PKNH_1256700; -.
DR   VEuPathDB; PlasmoDB:PKNH_1256700; -.
DR   HOGENOM; CLU_033144_2_2_1; -.
DR   InParanoid; B3L8F2; -.
DR   OMA; RSCAFCQ; -.
DR   OrthoDB; 575at2759; -.
DR   PhylomeDB; B3L8F2; -.
DR   UniPathway; UPA00538; UER00593.
DR   Proteomes; UP000031513; Chromosome 12.
DR   GO; GO:0020011; C:apicoplast; 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   SFLD; SFLDF00271; lipoyl_synthase; 1.
DR   SFLD; SFLDS00029; Radical_SAM; 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; Apicoplast; Iron; Iron-sulfur; Metal-binding; Plastid;
KW   Reference proteome; S-adenosyl-L-methionine; Signal; Transferase.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03123"
FT   CHAIN           24..442
FT                   /note="Lipoyl synthase, apicoplast"
FT                   /id="PRO_0000398231"
FT   DOMAIN          189..407
FT                   /note="Radical SAM core"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT   REGION          104..154
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        106..154
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         177
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         182
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         188
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         203
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         207
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         210
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         418
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   442 AA;  50641 MW;  4295AD91FB6F56A4 CRC64;
     MRVLTPSLYI YAFFIFCVRF KCGNRTTVAS AIRASYDMPP KELRVGDMLK KTSQPNCNYR
     TRGKCRKFFF VWKLDKMRDA HLGVQAKRRK NHLRSGSATY EASLGEHQLK GKRKESATNV
     EKEKKEKEQQ EERLPVPKVG NKMPEKKPDW FHVPAPTGKK YNKLKEDLKK LKLHTVCEEA
     QCPNIGECWN IGTATIMLLG DTCTRGCKFC SIKTSSKPLA PDANEPFNTA KAICEWDINY
     VVLTSVDRDD LPDGGASHFA KTIELIKFSR PEILIECLVS DFQGNVDSIR KLANSGMEVY
     AHNIETVRRL QKFVRDRRAN YEQSLRVLKI AKEINPMLYT KTSIMLGLGE TKEEVLEAMS
     DVRQHNIDVI TFGQYLRPTK NHLNVVEYVS PQMFDFYKEE GMKMGFKYIA SGPLVRSSYK
     AGEYFMKSLV EQRRGAKTHA QG
//