Top Level Name

  ⌊ Superfamily (core) Radical SAM

    ⌊ Subgroup lipoyl synthase like

Family known
Total 100% <100% Family unknown
Functional domains 5416 5331 37 48
UniProtKB 19194 0 19141 53
GI 35064 34849 189 26
Structures 5
Reactions 0
Functional domains of this subgroup were last updated on June 10, 2017
New functional domains were last added to this subgroup on Oct. 7, 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

Lanz ND, Pandelia ME, Kakar ES, Lee KH, Krebs C, Booker SJ

Evidence for a Catalytically and Kinetically Competent Enzyme-Substrate Cross-linked Intermediate in Catalysis by Lipoyl Synthase

▸ Abstract

Biochemistry 2014;53(28):4557-4572 | PubMed ID: 24901788

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

The enzymes are annotated as being of the TIM Barrel ( fold by Gene3D. At an E-Value of 1E-75, this group of proteins remains as a single cluster with a few singletons, many of which are fragments.

Sequence Similarity Networks

Download a Sequence Similarity Network of this subgroup (XGMML format ).

Network downloads are XGMML files that are readable by program such as Cytoscape. In these networks, nodes represent proteins and edges represent pairwise similarities better than a given edge-score cutoff. The edge score is either a bit score for full networks or mean E values for a Repnet. Additionally, these networks contain several attributes with data from the SFLD.

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List of files included in the download. A detailed list of included node attributes, their definitions, and their uses [revised: 1/24/2014].

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Multiple Sequence Alignment

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Multiple Sequence Alignment

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Data Type All (#) Known (#) Unknown (#)
Full length FASTA (5416) (5368) (48)
Complete annotation (.tsv) (5416) (5368) (48)
Annotation suitable for Excel ® (.tsv) (5416) (5368) (48)
Clear form

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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:
 →Network (multiple file types)
Download the annotation of all sequences as shown in the table below as a ͟Tab ͟Separated ͟Value (TSV) file. This file can be imported into a spreadsheet application.
Full length FASTA
Full length sequences in FASTA format.
Functional Domain FASTA
Sequences of the Functional Domain in FASTA format.
Complete annotation
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.
Total number of functional domains in this group.
Number of Functional Domains that have been manually or automatically been assigned to a family.
Number of Functional Domains that have not been assigned to a family.
Number of structures available from the PDB for members of this group.
Number of Functional Domains with 100% of Conserved Residues
Number of Functional Domains with less than 100% Conserved Residues
Subgroup ▸ Legend T K C U S
lipoyl synthase like 5416 5368 5331 48 5
┗ lipoyl synthase 5368 5368 5331 2
Depth of the multi-level Subgroup hierarchy.