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Information on EC 2.8.1.8 - lipoyl synthase

for references in articles please use BRENDA:EC2.8.1.8

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IUBMB Comments

This enzyme catalyses the final step in the de-novo biosynthesis of the lipoyl cofactor, the attachment of two sulfhydryl groups to C6 and C8 of a pendant octanoyl chain. It is a member of the ‘AdoMet radical’ (radical SAM) family, all members of which produce the 5′-deoxyadenosin-5′-yl radical and methionine from AdoMet (S-adenosylmethionine) by the addition of an electron from an iron-sulfur centre. The enzyme contains two [4Fe-4S] clusters. The first cluster produces the radicals, which are converted into 5′-deoxyadenosine when they abstract hydrogen atoms from C6 and C8, respectively, leaving reactive radicals at these positions that interact with sulfur atoms within the second (auxiliary) cluster. Having donated two sulfur atoms, the auxiliary cluster is degraded during catalysis, but is regenerated immediately by the transfer of a new cluster from iron-sulfur cluster carrier proteins . Lipoylation is essential for the function of several key enzymes involved in oxidative metabolism, as it converts apoprotein into the biologically active holoprotein. Examples of such lipoylated proteins include pyruvate dehydrogenase (E2 domain), 2-oxoglutarate dehydrogenase (E2 domain), the branched-chain 2-oxoacid dehydrogenases and the glycine cleavage system (H protein) [1,2]. An alternative lipoylation pathway involves EC 6.3.1.20, lipoate—protein ligase, which can lipoylate apoproteins using exogenous lipoic acid (or its analogues) .

The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
  • 2.8.1.8
  • lipoylation
  • lipas
  • lipoic
  • iron-sulfur
  • octanoyl
  • 5\'-deoxyadenosyl
  • octanoyl-acp
  • octanoyltransferase
  • methylthiolation
  • 5'-radical
  • h-protein
Reaction Schemes
[protein]-N6-(octanoyl)-L-lysine
+
an [Fe-S] cluster scaffold protein carrying a [4Fe-4S]2+ cluster
+
2
+
2
+
6
=
[protein]-N6-[(R)-dihydrolipoyl]-L-lysine
+
an [Fe-S] cluster scaffold protein
+
2
+
4
+
2
+
2
+
2

Synonyms
lipoyl synthase, lipoate synthase, lip1p, lips2, tk2109, tk2248, lipa protein, lips1, more

REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
[protein]-N6-(octanoyl)-L-lysine + an [Fe-S] cluster scaffold protein carrying a [4Fe-4S]2+ cluster + 2 S-adenosyl-L-methionine + 2 oxidized [2Fe-2S] ferredoxin + 6 H+ = [protein]-N6-[(R)-dihydrolipoyl]-L-lysine + an [Fe-S] cluster scaffold protein + 2 sulfide + 4 Fe3+ + 2 L-methionine + 2 5'-deoxyadenosine + 2 reduced [2Fe-2S] ferredoxin
show the reaction diagram
PATHWAY SOURCE
PATHWAYS
MetaCyc
lipoate biosynthesis and incorporation I, lipoate biosynthesis and incorporation II, lipoate biosynthesis and incorporation III (Bacillus), lipoate biosynthesis and incorporation IV (yeast), lipoate biosynthesis and incorporation V (mammals)
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