ID   LIAS_PICSI              Reviewed;         386 AA.
AC   A9NNH7;
DT   05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT   05-FEB-2008, sequence version 1.
DT   24-JAN-2024, entry version 60.
DE   RecName: Full=Lipoyl synthase, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03128};
DE            EC=2.8.1.8 {ECO:0000255|HAMAP-Rule:MF_03128};
DE   AltName: Full=Lipoate synthase {ECO:0000255|HAMAP-Rule:MF_03128};
DE            Short=LS {ECO:0000255|HAMAP-Rule:MF_03128};
DE            Short=Lip-syn {ECO:0000255|HAMAP-Rule:MF_03128};
DE   AltName: Full=Lipoic acid synthase {ECO:0000255|HAMAP-Rule:MF_03128};
GN   Name=LIP1 {ECO:0000255|HAMAP-Rule:MF_03128};
OS   Picea sitchensis (Sitka spruce) (Pinus sitchensis).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Pinopsida; Pinidae; Conifers I; Pinales; Pinaceae; Picea.
OX   NCBI_TaxID=3332;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=18854048; DOI=10.1186/1471-2164-9-484;
RA   Ralph S.G., Chun H.J.E., Kolosova N., Cooper D., Oddy C., Ritland C.E.,
RA   Kirkpatrick R., Moore R., Barber S., Holt R.A., Jones S.J.M., Marra M.A.,
RA   Douglas C.J., Ritland K., Bohlmann J.;
RT   "A conifer genomics resource of 200,000 spruce (Picea spp.) ESTs and 6,464
RT   high-quality, sequence-finished full-length cDNAs for Sitka spruce (Picea
RT   sitchensis).";
RL   BMC Genomics 9:484-484(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_03128}.
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_03128};
CC   -!- COFACTOR:
CC       Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_03128};
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_03128};
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_03128}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03128}.
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_03128}.
CC   -!- SIMILARITY: Belongs to the radical SAM superfamily. Lipoyl synthase
CC       family. {ECO:0000255|HAMAP-Rule:MF_03128}.
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DR   EMBL; EF082836; ABK22188.1; -; mRNA.
DR   AlphaFoldDB; A9NNH7; -.
DR   SMR; A9NNH7; -.
DR   UniPathway; UPA00538; UER00593.
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   HAMAP; MF_03128; Lipoyl_synth_plantM; 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; IPR027527; Lipoyl_synth_mt.
DR   InterPro; IPR007197; rSAM.
DR   NCBIfam; TIGR00510; lipA; 1.
DR   PANTHER; PTHR10949; LIPOYL SYNTHASE; 1.
DR   PANTHER; PTHR10949:SF36; 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   2: Evidence at transcript level;
KW   4Fe-4S; Iron; Iron-sulfur; Metal-binding; Mitochondrion;
KW   S-adenosyl-L-methionine; Transferase.
FT   CHAIN           1..386
FT                   /note="Lipoyl synthase, mitochondrial"
FT                   /id="PRO_0000398853"
FT   DOMAIN          131..351
FT                   /note="Radical SAM core"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT   BINDING         115
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03128"
FT   BINDING         120
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03128"
FT   BINDING         126
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03128"
FT   BINDING         146
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_03128"
FT   BINDING         150
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_03128"
FT   BINDING         153
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_03128"
FT   BINDING         362
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03128"
SQ   SEQUENCE   386 AA;  42579 MW;  0FAA92A285A950F8 CRC64;
     MSINPAFLRR ITWGSKSLHH QFTRCQVRAL SSSVEQTPES TTPALSALRE RLANGGPTLS
     DFLTRNLGEE PYSVDVGTKK NPLPKPKWMK AAVPGGDKYT AIKAKLREMN LHTVCEEAKC
     PNLGECWSGG ETGTATATIM ILGDTCTRGC RFCAVKTSRT PPPPDPNEPT NVAEAIVSWG
     LDYVVLTSVD RDDLPDQGSG HFAKTVQKLK QLKPKMLVEA LVPDFQGNSE CVQKVATSGL
     DVFAHNIETV EELQRVVRDH RANFNQSLEV LKMAKTYSPL GVLTKTSVML GCGETPAQVI
     ETMEKVREAG VDVITFGQYM RPTKRHMAVS EYVTPEAFEK YQKLGMEMGF RYVASGPMVR
     SSYKAGEFYI KSMIEDDRKK ASSSSI
//