Top Level Name

  ⌊ Superfamily (core) Radical SAM

    ⌊ Subgroup lipoyl synthase like

     ⌊ Family lipoyl synthase

Total 100% <100%
Functional domains 5368 5331 37
UniProtKB 19141 19097 44
GI 35038 34849 189
Structures 2
Reactions 1
Functional domains of this family were last updated on June 10, 2017
New functional domains were last added to this family on July 5, 2014

This group of enzymes catalyse the final step in the de-novo biosynthesis of the lipoyl cofactor, with the other enzyme involved being EC, lipoyl(octanoyl) transferase. Lipoyl synthase enzymes require two SAM molecules and are stoichiometric in nature.

As a member of the Radical SAM superfamily lipoyl synthase enzymes ustilise S-adenosylmethionine (SAM) to create a 5′-deoxyadenosinyl radical and methionine, by the addition of an electron from an iron-sulfur centre. The radical is converted into 5′-deoxyadenosine when it abstracts a hydrogen atom from C-6 and C-8 consecutively. Recent experimental evidence suggests that the proton is abstracted from C-6 first, resulting in an enzyme-bound intermediate. A second SAM molecule is then reduced which abstracts the proton from C-8. The mechanism results in an inversion of configuration.

Miller JR, Busby RW, Jordan SW, Cheek J, Henshaw TF, Ashley GW, Broderick JB, Cronan JE Jr, Marletta MA

Escherichia coli LipA is a lipoyl synthase: in vitro biosynthesis of lipoylated pyruvate dehydrogenase complex from octanoyl-acyl carrier protein

▸ Abstract

Biochemistry 2000;39(49):15166-15178 | PubMed ID: 11106496

Zhao X, Miller JR, Jiang Y, Marletta MA, Cronan JE

Assembly of the covalent linkage between lipoic acid and its cognate enzymes

▸ Abstract

Chem Biol. 2003;10(12):1293-1302 | PubMed ID: 14700636

Cicchillo RM, Iwig DF, Jones AD, Nesbitt NM, Baleanu-Gogonea C, Souder MG, Tu L, Booker SJ

Lipoyl synthase requires two equivalents of S-adenosyl-L-methionine to synthesize one equivalent of lipoic acid

▸ Abstract

Biochemistry 2004;43(21):6378-6386 | PubMed ID: 15157071

Cicchillo RM, Lee KH, Baleanu-Gogonea C, Nesbitt NM, Krebs C, Booker SJ.

Escherichia coli lipoyl synthase binds two distinct [4Fe-4S] clusters per polypeptide.

▸ Abstract

Biochemistry 2004;43(37):11770-11781 | PubMed ID: 15362861

Cicchillo RM, Booker SJ.

Mechanistic investigations of lipoic acid biosynthesis in Escherichia coli: both sulfur atoms in lipoic acid are contributed by the same lipoyl synthase polypeptide.

▸ Abstract

J Am Chem Soc. 2005;127(9):2860-2861 | PubMed ID: 15740115

Booker SJ

Unraveling the pathway of lipoic acid biosynthesis

▸ Abstract

Chem Biol. 2004;11(1):10-12 | PubMed ID: 15112987

Harmer JE, Hiscox MJ, Dinis PC, Fox SJ, Iliopoulos A, Hussey JE, Sandy J, Van Beek FT, Essex JW, Roach PL

Structures of lipoyl synthase reveal a compact active site for controlling sequential sulfur insertion reactions

▸ Abstract

Biochem J 2014;None(None):None-None | PubMed ID: 25100160

Cronan JE

The structure of lipoyl synthase, a remarkable enzyme that performs the last step of an extraordinary biosynthetic pathway

▸ Abstract

Biochem J 2014;464(1):None-None | PubMed ID: 25341020

McLaughlin MI, Lanz ND, Goldman PJ, Lee KH, Booker SJ, Drennan CL

Crystallographic snapshots of sulfur insertion by lipoyl synthase

▸ Abstract

Proc Natl Acad Sci U S A 2016;113(34):9446-9450 | PubMed ID: 27506792

Lanz ND, Rectenwald JM, Wang B, Kakar ES, Laremore TN, Booker SJ, Silakov A

Characterization of a Radical Intermediate in Lipoyl Cofactor Biosynthesis

▸ Abstract

J Am Chem Soc 2015;137(41):13216-13219 | PubMed ID: 26390103

No notes.

Sequence Similarity Networks

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Multiple Sequence Alignment

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Multiple Sequence Alignment

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Cutoff Value
The least significant edge-score at which pairwise similarities are included in the network. A bit score for the full network, or a mean E value for the Repnet.
XGMML format
Open in Cytoscape via:
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Full length sequences in FASTA format.
Functional Domain FASTA
Sequences of the Functional Domain in FASTA format.
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Download complete annotation of sequences sets of this superfamily as a ͟Tab ͟Separated ͟Value (TSV) file. This file has all data but cell size can exceed the maximum supported by spreadsheet programs (such as Microsoft Excel ®).
Spreadsheet ready annotation
Annotation of sequences sets of this superfamily in a ͟Tab ͟Separated ͟Value (TSV) file. This file can be imported into a spreadsheet application. Cells which exceed the allowed spreadsheet maximum (32.5K) are preceded by the word "Truncated" and clipped short.
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Number of Functional Domains that have been manually or automatically been assigned to a family.
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Number of Functional Domains with 100% of Conserved Residues
Number of Functional Domains with less than 100% Conserved Residues

Active Site

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Catalyzed Reaction(s)

lipoyl synthase

+ 2 + + 2 2 + 2 + + 2 + 2
thiol group
S-adenosyl-L-methionine zwitterion
N(6)-octanoyl-L-lysine residue
H group
N(6)-[(R)-lipoyl]-L-lysine residue
L-methionine zwitterion

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