Lipoyl synthase (P60716)

Identification
Name:Lipoyl synthase
Synonyms:
  • Lip-syn
  • LS
  • Lipoate synthase
  • Lipoic acid synthase
  • Sulfur insertion protein lipA
Gene Name:lipA
Enzyme Class:
Biological Properties
General Function:Involved in catalytic activity
Specific Function:Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes, thereby converting the octanoylated domains into lipoylated derivatives. Free octanoate is not a substrate for lipA
Cellular Location:Cytoplasm
SMPDB Pathways:
KEGG Pathways:
KEGG Reactions:
1.0Protein N6-(octanoyl)lysine+2.0Sulfur donor+2.0Thumb+1.0Protein N6-(octanoyl)lysine ↔ 1.0Protein N6-(lipoyl)lysine+2.0Thumb+2.0Thumb+1.0Protein N6-(lipoyl)lysine
1.0Protein N6-(octanoyl)lysine + 2.0Sulfur donor + 2.0S-Adenosylmethionine + 1.0Protein N6-(octanoyl)lysine ↔ 1.0Protein N6-(lipoyl)lysine + 2.0L-Methionine + 2.05'-Deoxyadenosine + 1.0Protein N6-(lipoyl)lysine
ReactionCard
1.0Octanoyl-[acp]+2.0Sulfur donor+2.0Thumb ↔ 1.0Lipoyl-[acp]+2.0Thumb+2.0Thumb
1.0Octanoyl-[acp] + 2.0Sulfur donor + 2.0S-Adenosylmethionine ↔ 1.0Lipoyl-[acp] + 2.0L-Methionine + 2.05'-Deoxyadenosine
ReactionCard
SMPDB Reactions:
1.0Octanoyl-[acyl-carrier protein] +2.0a sulfur donor+2.0S-adenosyl-L-methionine → 1.0Lipoyl-ACP+2.0Thumb+1.0Thumb
1.0Octanoyl-[acyl-carrier protein] + 2.0a sulfur donor + 2.0S-adenosyl-L-methionine → 1.0Lipoyl-ACP + 2.0L-Methionine + 1.05'-Deoxyadenosine
ReactionCard
1.0Protein N6-(octanoyl)lysine+2.0a sulfur donor+2.0S-adenosyl-L-methionine → 1.0Protein N6-(lipoyl)lysine+2.0Thumb+2.0Thumb
1.0Protein N6-(octanoyl)lysine + 2.0a sulfur donor + 2.0S-adenosyl-L-methionine → 1.0Protein N6-(lipoyl)lysine + 2.0L-Methionine + 2.05'-Deoxyadenosine
ReactionCard
1.0a [lipoyl-carrier protein] N6-octanoyl-L-lysine+2.0S-adenosyl-L-methionine+2.0a sulfurated [sulfur carrier] +2.0Reduced ferredoxin → 1.0Protein N6-(lipoyl)lysine+2.0Thumb+2.0Thumb+2.0an unsulfurated [sulfur carrier]+2.0Oxidized ferredoxin
1.0a [lipoyl-carrier protein] N6-octanoyl-L-lysine + 2.0S-adenosyl-L-methionine + 2.0a sulfurated [sulfur carrier]  + 2.0Reduced ferredoxin → 1.0Protein N6-(lipoyl)lysine + 2.05'-Deoxyadenosine + 2.0L-Methionine + 2.0an unsulfurated [sulfur carrier] + 2.0Oxidized ferredoxin
ReactionCard
Complex Reactions:
1.0[4Fe-4S] iron-sulfur cluster+2.0Thumb+1.0Thumb+1.0Thumb+1.0octanoate (protein bound) → 1.0[2Fe-2S] iron-sulfur cluster+2.0Thumb+2.0Thumb+1.0lipoate (protein bound)+2.0Thumb+1.0Thumb
1.0[4Fe-4S] iron-sulfur cluster + 2.0S-Adenosylmethionine + 1.0Hydrogen ion + 1.0NAD + 1.0octanoate (protein bound) → 1.0[2Fe-2S] iron-sulfur cluster + 2.05'-Deoxyadenosine + 2.0Iron + 1.0lipoate (protein bound) + 2.0L-Methionine + 1.0NADH
ReactionCard
Metabolites:
ECMDB IDNameView
ECMDB211745'-DeoxyadenosineMetaboCard
ECMDB21225Hydrogen ionMetaboCard
ECMDB03276Hydrogen sulfideMetaboCard
ECMDB00692IronMetaboCard
ECMDB00696L-MethionineMetaboCard
ECMDB00902NADMetaboCard
ECMDB01487NADHMetaboCard
ECMDB01185S-AdenosylmethionineMetaboCard
GO Classification:
Function
4 iron, 4 sulfur cluster binding
binding
catalytic activity
iron-sulfur cluster binding
lipoate synthase activity
metal cluster binding
sulfurtransferase activity
transferase activity
transferase activity, transferring sulfur-containing groups
Process
cellular metabolic process
coenzyme metabolic process
cofactor metabolic process
lipoate biosynthetic process
lipoic acid biosynthetic process
lipoic acid metabolic process
metabolic process
Gene Properties
Blattner:b0628
Gene OrientationCounterclockwise
Centisome Percentage:14.19
Left Sequence End658474
Right Sequence End659439
Gene Sequence:
>966 bp
ATGAGTAAACCCATTGTGATGGAACGCGGTGTTAAATACCGCGATGCCGATAAGATGGCC
CTTATCCCGGTTAAAAACGTGGCAACAGAGCGCGAAGCCCTGCTGCGCAAGCCGGAATGG
ATGAAAATCAAGCTTCCAGCGGACTCTACACGTATCCAGGGCATCAAAGCCGCAATGCGC
AAAAATGGCCTGCATTCTGTCTGCGAGGAAGCCTCCTGCCCTAACCTGGCGGAATGCTTC
AACCACGGCACAGCAACGTTTATGATCCTCGGCGCTATTTGTACCCGCCGTTGTCCGTTC
TGTGATGTTGCCCACGGTCGCCCGGTAGCTCCTGATGCCAATGAACCAGTGAAACTGGCG
CAGACCATTGCCGATATGGCGCTGCGTTATGTGGTTATCACCTCCGTTGACCGTGATGAC
CTGCGCGATGGCGGTGCCCAGCACTTTGCGGATTGCATTACTGCCATTCGGGAAAAAAGC
CCGCAAATCAAAATTGAAACTCTGGTGCCGGATTTCCGCGGTCGTATGGATCGTGCTCTG
GATATTCTGACTGCAACGCCACCAGATGTGTTCAACCATAACCTGGAAAACGTACCGCGT
ATTTACCGTCAGGTACGGCCTGGTGCAGATTACAACTGGTCGCTGAAGCTGCTGGAACGC
TTTAAAGAAGCGCATCCGGAAATCCCGACCAAGTCTGGTCTGATGGTGGGACTGGGTGAA
ACCAATGAAGAAATTATTGAGGTAATGCGCGACCTGCGCCGTCATGGTGTGACGATGTTA
ACGCTGGGGCAATATTTGCAGCCAAGCCGCCATCACCTGCCGGTTCAACGTTACGTTAGC
CCGGATGAGTTCGACGAAATGAAAGCCGAAGCGCTGGCGATGGGCTTTACCCATGCTGCA
TGCGGTCCGTTTGTCCGCTCTTCTTACCACGCCGATTTGCAGGCGAAAGGGATGGAAGTT
AAGTAA
Protein Properties
Pfam Domain Function:
Protein Residues:321
Protein Molecular Weight:36071
Protein Theoretical pI:8
Signaling Regions:
  • None
Transmembrane Regions:
  • None
Protein Sequence:
>Lipoyl synthase
MSKPIVMERGVKYRDADKMALIPVKNVATEREALLRKPEWMKIKLPADSTRIQGIKAAMR
KNGLHSVCEEASCPNLAECFNHGTATFMILGAICTRRCPFCDVAHGRPVAPDANEPVKLA
QTIADMALRYVVITSVDRDDLRDGGAQHFADCITAIREKSPQIKIETLVPDFRGRMDRAL
DILTATPPDVFNHNLENVPRIYRQVRPGADYNWSLKLLERFKEAHPEIPTKSGLMVGLGE
TNEEIIEVMRDLRRHGVTMLTLGQYLQPSRHHLPVQRYVSPDEFDEMKAEALAMGFTHAA
CGPFVRSSYHADLQAKGMEVK
References
External Links:
ResourceLink
Uniprot ID:P60716
Uniprot Name:LIPA_ECOLI
GenBank Gene ID:AP009048
Genebank Protein ID:1651257
Ecogene ID:EG11306
Ecocyc:EG11306
ColiBase:b0628
Kegg Gene:b0628
EchoBASE ID:EB1283
CCDB:LIPA_ECOLI
BacMap:16128611
General Reference:
  • Blattner, F. R., Plunkett, G. 3rd, Bloch, C. A., Perna, N. T., Burland, V., Riley, M., Collado-Vides, J., Glasner, J. D., Rode, C. K., Mayhew, G. F., Gregor, J., Davis, N. W., Kirkpatrick, H. A., Goeden, M. A., Rose, D. J., Mau, B., Shao, Y. (1997). "The complete genome sequence of Escherichia coli K-12." Science 277:1453-1462. Pubmed: 9278503
  • Booker, S. J. (2004). "Unraveling the pathway of lipoic acid biosynthesis." Chem Biol 11:10-12. Pubmed: 15112987
  • Cicchillo, R. M., Booker, S. J. (2005). "Mechanistic investigations of lipoic acid biosynthesis in Escherichia coli: both sulfur atoms in lipoic acid are contributed by the same lipoyl synthase polypeptide." J Am Chem Soc 127:2860-2861. Pubmed: 15740115
  • Cicchillo, R. M., Iwig, D. F., Jones, A. D., Nesbitt, N. M., Baleanu-Gogonea, C., Souder, M. G., Tu, L., Booker, S. J. (2004). "Lipoyl synthase requires two equivalents of S-adenosyl-L-methionine to synthesize one equivalent of lipoic acid." Biochemistry 43:6378-6386. Pubmed: 15157071
  • Cicchillo, R. M., Lee, K. H., Baleanu-Gogonea, C., Nesbitt, N. M., Krebs, C., Booker, S. J. (2004). "Escherichia coli lipoyl synthase binds two distinct [4Fe-4S] clusters per polypeptide." Biochemistry 43:11770-11781. Pubmed: 15362861
  • Hayashi, K., Morooka, N., Yamamoto, Y., Fujita, K., Isono, K., Choi, S., Ohtsubo, E., Baba, T., Wanner, B. L., Mori, H., Horiuchi, T. (2006). "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Mol Syst Biol 2:2006.0007. Pubmed: 16738553
  • Hayden, M. A., Huang, I., Bussiere, D. E., Ashley, G. W. (1992). "The biosynthesis of lipoic acid. Cloning of lip, a lipoate biosynthetic locus of Escherichia coli." J Biol Chem 267:9512-9515. Pubmed: 1577793
  • Miller, J. R., Busby, R. W., Jordan, S. W., Cheek, J., Henshaw, T. F., Ashley, G. W., Broderick, J. B., Cronan, J. E. Jr, Marletta, M. A. (2000). "Escherichia coli LipA is a lipoyl synthase: in vitro biosynthesis of lipoylated pyruvate dehydrogenase complex from octanoyl-acyl carrier protein." Biochemistry 39:15166-15178. Pubmed: 11106496
  • Oshima, T., Aiba, H., Baba, T., Fujita, K., Hayashi, K., Honjo, A., Ikemoto, K., Inada, T., Itoh, T., Kajihara, M., Kanai, K., Kashimoto, K., Kimura, S., Kitagawa, M., Makino, K., Masuda, S., Miki, T., Mizobuchi, K., Mori, H., Motomura, K., Nakamura, Y., Nashimoto, H., Nishio, Y., Saito, N., Horiuchi, T., et, a. l. .. (1996). "A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map." DNA Res 3:137-155. Pubmed: 8905232
  • Reed, K. E., Cronan, J. E. Jr (1993). "Lipoic acid metabolism in Escherichia coli: sequencing and functional characterization of the lipA and lipB genes." J Bacteriol 175:1325-1336. Pubmed: 8444795
  • Zhao, X., Miller, J. R., Jiang, Y., Marletta, M. A., Cronan, J. E. (2003). "Assembly of the covalent linkage between lipoic acid and its cognate enzymes." Chem Biol 10:1293-1302. Pubmed: 14700636