LIPA_MYCTU
ID LIPA_MYCTU Reviewed; 311 AA.
AC P9WK91; L0T964; P65283; Q10380;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=Lipoyl synthase {ECO:0000255|HAMAP-Rule:MF_00206, ECO:0000303|PubMed:26841001};
DE EC=2.8.1.8 {ECO:0000255|HAMAP-Rule:MF_00206};
DE AltName: Full=Lip-syn {ECO:0000255|HAMAP-Rule:MF_00206};
DE Short=LS {ECO:0000255|HAMAP-Rule:MF_00206};
DE AltName: Full=Lipoate synthase {ECO:0000255|HAMAP-Rule:MF_00206};
DE AltName: Full=Lipoic acid synthase {ECO:0000255|HAMAP-Rule:MF_00206};
DE AltName: Full=Sulfur insertion protein LipA {ECO:0000255|HAMAP-Rule:MF_00206};
GN Name=lipA {ECO:0000255|HAMAP-Rule:MF_00206, ECO:0000303|PubMed:26841001};
GN OrderedLocusNames=Rv2218; ORFNames=MTCY190.29;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND INTERACTION WITH GCVH.
RX PubMed=26841001; DOI=10.1021/acs.biochem.5b01216;
RA Lanz N.D., Lee K.H., Horstmann A.K., Pandelia M.E., Cicchillo R.M.,
RA Krebs C., Booker S.J.;
RT "Characterization of lipoyl synthase from Mycobacterium tuberculosis.";
RL Biochemistry 55:1372-1383(2016).
RN [4] {ECO:0007744|PDB:5EXI, ECO:0007744|PDB:5EXJ, ECO:0007744|PDB:5EXK}
RP X-RAY CRYSTALLOGRAPHY (1.64 ANGSTROMS) IN COMPLEXES WITH IRON-SULFUR;
RP SUBSTRATES AND PRODUCTS, AND COFACTOR.
RX PubMed=27506792; DOI=10.1073/pnas.1602486113;
RA McLaughlin M.I., Lanz N.D., Goldman P.J., Lee K.H., Booker S.J.,
RA Drennan C.L.;
RT "Crystallographic snapshots of sulfur insertion by lipoyl synthase.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:9446-9450(2016).
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_00206, ECO:0000269|PubMed:26841001}.
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_00206,
CC ECO:0000269|PubMed:26841001};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00206,
CC ECO:0000269|PubMed:26841001};
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_00206, ECO:0000269|PubMed:26841001,
CC ECO:0000269|PubMed:27506792};
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_00206}.
CC -!- SUBUNIT: Forms a complex with GcvH, the H protein of the glycine
CC cleavage system. The strength of association is dependent on the
CC presence of S-adenosyl-L-methionine. {ECO:0000269|PubMed:26841001}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00206}.
CC -!- SIMILARITY: Belongs to the radical SAM superfamily. Lipoyl synthase
CC family. {ECO:0000255|HAMAP-Rule:MF_00206}.
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DR EMBL; AL123456; CCP44995.1; -; Genomic_DNA.
DR PIR; C70787; C70787.
DR RefSeq; NP_216734.1; NC_000962.3.
DR RefSeq; WP_003411460.1; NZ_NVQJ01000008.1.
DR PDB; 5EXI; X-ray; 2.28 A; A=1-311.
DR PDB; 5EXJ; X-ray; 1.64 A; A=1-311.
DR PDB; 5EXK; X-ray; 1.86 A; A/C/E/G/I/K=1-311.
DR PDBsum; 5EXI; -.
DR PDBsum; 5EXJ; -.
DR PDBsum; 5EXK; -.
DR AlphaFoldDB; P9WK91; -.
DR SMR; P9WK91; -.
DR STRING; 83332.Rv2218; -.
DR PaxDb; P9WK91; -.
DR DNASU; 887922; -.
DR GeneID; 45426194; -.
DR GeneID; 887922; -.
DR KEGG; mtu:Rv2218; -.
DR TubercuList; Rv2218; -.
DR eggNOG; COG0320; Bacteria.
DR OMA; PYCDIDF; -.
DR PhylomeDB; P9WK91; -.
DR BRENDA; 2.8.1.8; 3445.
DR UniPathway; UPA00538; UER00593.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; 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 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Cytoplasm; Iron; Iron-sulfur; Metal-binding;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..311
FT /note="Lipoyl synthase"
FT /id="PRO_0000102326"
FT DOMAIN 67..281
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT BINDING 55
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00206,
FT ECO:0000269|PubMed:27506792, ECO:0007744|PDB:5EXI,
FT ECO:0007744|PDB:5EXJ"
FT BINDING 60
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00206,
FT ECO:0000269|PubMed:27506792, ECO:0007744|PDB:5EXI,
FT ECO:0007744|PDB:5EXJ"
FT BINDING 66
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00206,
FT ECO:0000269|PubMed:27506792, ECO:0007744|PDB:5EXI,
FT ECO:0007744|PDB:5EXJ"
FT BINDING 81
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_00206,
FT ECO:0000269|PubMed:27506792, ECO:0007744|PDB:5EXI,
FT ECO:0007744|PDB:5EXJ, ECO:0007744|PDB:5EXK"
FT BINDING 85
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_00206,
FT ECO:0000269|PubMed:27506792, ECO:0007744|PDB:5EXI,
FT ECO:0007744|PDB:5EXJ, ECO:0007744|PDB:5EXK"
FT BINDING 88
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_00206,
FT ECO:0000269|PubMed:27506792, ECO:0007744|PDB:5EXI,
FT ECO:0007744|PDB:5EXJ, ECO:0007744|PDB:5EXK"
FT BINDING 292
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00206,
FT ECO:0000269|PubMed:27506792, ECO:0007744|PDB:5EXI,
FT ECO:0007744|PDB:5EXJ"
FT HELIX 5..17
FT /evidence="ECO:0007829|PDB:5EXK"
FT HELIX 37..49
FT /evidence="ECO:0007829|PDB:5EXJ"
FT HELIX 54..57
FT /evidence="ECO:0007829|PDB:5EXJ"
FT HELIX 63..68
FT /evidence="ECO:0007829|PDB:5EXJ"
FT STRAND 71..77
FT /evidence="ECO:0007829|PDB:5EXJ"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:5EXJ"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:5EXJ"
FT HELIX 102..113
FT /evidence="ECO:0007829|PDB:5EXJ"
FT STRAND 116..122
FT /evidence="ECO:0007829|PDB:5EXJ"
FT TURN 129..132
FT /evidence="ECO:0007829|PDB:5EXJ"
FT HELIX 133..146
FT /evidence="ECO:0007829|PDB:5EXJ"
FT STRAND 151..155
FT /evidence="ECO:0007829|PDB:5EXJ"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:5EXJ"
FT HELIX 163..171
FT /evidence="ECO:0007829|PDB:5EXJ"
FT STRAND 175..178
FT /evidence="ECO:0007829|PDB:5EXJ"
FT HELIX 185..191
FT /evidence="ECO:0007829|PDB:5EXJ"
FT HELIX 197..209
FT /evidence="ECO:0007829|PDB:5EXJ"
FT STRAND 213..223
FT /evidence="ECO:0007829|PDB:5EXJ"
FT HELIX 226..238
FT /evidence="ECO:0007829|PDB:5EXJ"
FT STRAND 243..248
FT /evidence="ECO:0007829|PDB:5EXJ"
FT HELIX 265..278
FT /evidence="ECO:0007829|PDB:5EXJ"
FT STRAND 281..286
FT /evidence="ECO:0007829|PDB:5EXJ"
FT TURN 291..294
FT /evidence="ECO:0007829|PDB:5EXJ"
FT HELIX 295..309
FT /evidence="ECO:0007829|PDB:5EXJ"
SQ SEQUENCE 311 AA; 34719 MW; 0594BBC9AB4A547A CRC64;
MSVAAEGRRL LRLEVRNAQT PIERKPPWIK TRARIGPEYT ELKNLVRREG LHTVCEEAGC
PNIFECWEDR EATFLIGGDQ CTRRCDFCQI DTGKPAELDR DEPRRVADSV RTMGLRYATV
TGVARDDLPD GGAWLYAATV RAIKELNPST GVELLIPDFN GEPTRLAEVF ESGPEVLAHN
VETVPRIFKR IRPAFTYRRS LGVLTAARDA GLVTKSNLIL GLGETSDEVR TALGDLRDAG
CDIVTITQYL RPSARHHPVE RWVKPEEFVQ FARFAEGLGF AGVLAGPLVR SSYRAGRLYE
QARNSRALAS R
