Top Level Name

  ⌊ Superfamily (core) Radical SAM

    ⌊ Subgroup BATS domain containing

  biotin synthase like

     ⌊ Family biotin synthase

Total 100% <100%
Functional domains 3245 3245 0
UniProtKB 9873 9873 0
GI 18996 18996 0
Structures 1
Reactions 1
Functional domains of this family were last updated on June 10, 2017
New functional domains were last added to this family on Oct. 7, 2014

The enzyme binds a [4Fe-4S] and a [2Fe-2S] cluster. In every reaction cycle, the enzyme consumes two molecules of AdoMet, each producing 5'-deoxyadenosine (dAH) and a putative dethiobiotinyl carbon radical. The first half reaction results in the hydrogen abstraction from C6 in dithiobiotin (DTB) and initial sulfur addition. Reaction with another equivalent of AdoMet results in abstraction of the C6 methylene pro-S hydrogen atom from 9-mercaptodethiobiotin (MTDB), and the resulting carbon radical is quenched via formation of an intramolecular C-S bond, thus closing the biotin thiophane ring. The sulfur donor [S] is believed to be the [2Fe-2S] cluster, which is sacrificed in the process, so that in vitro the reaction is a single turnover. In vivo, the [2Fe-2S] cluster can be reassembled by the Isc or Suf iron-sulfur cluster assembly systems, to allow further catalysis.

It has been demonstrated that biotin formation proceeds in a stepwise manner, with only one monomer within the dimeric enzyme undergoing turnover to form biotin. The second monomer binds substrates, but does not undergo a reaction, i.e. the enzyme is half-site active. Further, the dAH and methionine generated during the first half-reaction (conversion of DTB to MDTB) can competitively compete with AdoMet during the second half-reaction, preventing the conversion of MDTB to biotin.

Vey JL, Drennan CL.

Structural insights into radical generation by the radical SAM superfamily

▸ Abstract

Chem Rev. 2011;111(4):2487-2506 | PubMed ID: 21370834

Taylor AM, Stoll S, Britt RD, Jarrett JT.

Reduction of the [2Fe-2S] cluster accompanies formation of the intermediate 9-mercaptodethiobiotin in Escherichia coli biotin synthase

▸ Abstract

Biochemistry 2011;50(37):7953-7963 | PubMed ID: 21859080

Phalip V, Lemoine Y, Jeltsch JM.

Cloning of Schizosaccharomyces pombe bio2 by heterologous complementation of a Saccharomyces cerevisiae mutant

▸ Abstract

Curr Microbiol. 1999;39(6):348-350 | PubMed ID: 10525840

Lotierzo M, Tse Sum Bui B, Florentin D, Escalettes F, Marquet A.

Biotin synthase mechanism: an overview

▸ Abstract

Biochem Soc Trans. 2005;33(4):820-823 | PubMed ID: 16042606

No notes.

Sequence Similarity Networks

Download a Sequence Similarity Network of this family (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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Full sequence similarity network is not available for this superfamily due to its size.
Repnet: 50% ID (19-May-2017)

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 (#)
Full length FASTA (3245) ()
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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.
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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.
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

Active Site

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Catalyzed Reaction(s)

biotin synthase

+ 2 + + 2 + 2 + 2 + + 2
thiol group
S-adenosyl-L-methionine zwitterion
H group
L-methionine zwitterion

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