Summary: Biotin/lipoate A/B protein ligase family
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This is the Wikipedia entry entitled "Cofactor transferase family". More...
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Cofactor transferase family Edit Wikipedia article
|Cofactor transferase domain|
|SCOP2||1bia / SCOPe / SUPFAM|
|Bacterial lipoate protein ligase C-terminus|
|Biotin protein ligase C terminal domain|
|SCOP2||1bia / SCOPe / SUPFAM|
In molecular biology, the Cofactor transferase family is a family of protein domains that includes biotin protein ligases, lipoate-protein ligases A, octanoyl-(acyl carrier protein):protein N-octanoyltransferases, and lipoyl-protein:protein N-lipoyltransferases. The metabolism of the cofactors Biotin and lipoic acid share this family. They also share the target modification domain (Pfam PF00364), and the sulfur insertion enzyme (Pfam PF04055).
Biotin protein ligase (BPL) is the enzyme responsible for attaching biotin to a specific lysine at the biotin carboxyl carrier protein. Each organism likely has only one BPL protein. Biotin attachment is a two step reaction that results in the formation of an amide linkage between the carboxyl group of biotin and the epsilon-amino group of the modified lysine. Biotin attachment is required for biotin biosynthesis and utilization of free biotin.
Lipoate-protein ligase catalyses the formation of an amide linkage between lipoic acid and a specific lysine residue of the lipoyl domain of lipoate dependent enzymes. They are required for the utilization of free lipoic acid.
Octanoyl-(acyl carrier protein):protein N-octanoyltransferases, or octanoyltransferases, are required for lipoic acid biosynthesis. They transfer octanoate from the acyl carrier protein (ACP), part of fatty acid biosynthesis, to the specific lysine residue of lipoyl domains. Two octanoyltransferase isozymes exist in this superfamily.
Lipoyl-protein:protein N-lipoyltransferases, or lipoylamidotransferases, are required for lipoic acid metabolism in some organisms. They transfer lipoic acid or octanoate from lipoyl domains and transfer to other lipoyl domains. In Bacillus subtilis, the transfer is from the glycine cleavage system H protein, GcvH, to other lipoyl domains. This is because the octanoyltransferase of B. subtilis is specific for GcvH.
Octanoyltransferases and lipoyl-amidotransferases are single domain enzymes. Characterized lipoate protein ligases require an additional accessory domain (Pfam PF10437) to adenylate the acyl substrate. Biotin protein ligases have an additional C-terminal domain which participates in biotin adenylation and dimerization. Biotin protein ligases may also have an additional N-terminal domain required for DNA binding, although this domain is not always present.
- Wilson KP, Shewchuk LM, Brennan RG, Otsuka AJ, Matthews BW (October 1992). "Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains". Proc. Natl. Acad. Sci. U.S.A. 89 (19): 9257â€“61. doi:10.1073/pnas.89.19.9257. PMCÂ 50105. PMIDÂ 1409631.
- Reche PA (October 2000). "Lipoylating and biotinylating enzymes contain a homologous catalytic module". Protein Sci. 9 (10): 1922â€“9. doi:10.1110/ps.9.10.1922. PMCÂ 2144473. PMIDÂ 11106165.
- Chapman-Smith A, Cronan JE (September 1999). "The enzymatic biotinylation of proteins: a post-translational modification of exceptional specificity". Trends Biochem. Sci. 24 (9): 359â€“63. doi:10.1016/s0968-0004(99)01438-3. PMIDÂ 10470036.
- Morris TW, Reed KE, Cronan JE (June 1994). "Identification of the gene encoding lipoate-protein ligase A of Escherichia coli. Molecular cloning and characterization of the lplA gene and gene product". J. Biol. Chem. 269 (23): 16091â€“100. doi:10.1016/S0021-9258(17)33977-7. PMIDÂ 8206909.
- Cronan JE, Zhao X, Jiang Y (2005). Function, attachment and synthesis of lipoic acid in Escherichia coli. Adv. Microb. Physiol. Advances in Microbial Physiology. 50. pp.Â 103â€“46. doi:10.1016/S0065-2911(05)50003-1. ISBNÂ 9780120277506. PMIDÂ 16221579.
- Christensen QH, Cronan JE (2010). "Lipoic acid synthesis: a new family of octanoyltransferases generally annotated as lipoate protein ligases". Biochemistry. 49 (46): 10024â€“36. doi:10.1021/bi101215f. PMCÂ 2982868. PMIDÂ 20882995.
- Christensen QH, Martin N, Mansilla MC, de Mendoza D, Cronan JE (2011). "A novel amidotransferase required for lipoic acid cofactor assembly in Bacillus subtilis". Mol. Microbiol. 80 (2): 350â€“63. doi:10.1111/j.1365-2958.2011.07598.x. PMCÂ 3088481. PMIDÂ 21338421.
- Martin N, Christensen QH, Mansilla MC, Cronan JE, de Mendoza D (2011). "A novel two-gene requirement for the octanoyltransfer reaction of Bacillus subtilis lipoic acid biosynthesis". Mol. Microbiol. 80 (2): 335â€“49. doi:10.1111/j.1365-2958.2011.07597.x. PMCÂ 3086205. PMIDÂ 21338420.
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Biotin/lipoate A/B protein ligase family Provide feedback
This family includes biotin protein ligase, lipoate-protein ligase A and B. Biotin is covalently attached at the active site of certain enzymes that transfer carbon dioxide from bicarbonate to organic acids to form cellular metabolites. Biotin protein ligase (BPL) is the enzyme responsible for attaching biotin to a specific lysine at the active site of biotin enzymes. Each organism probably has only one BPL. Biotin attachment is a two step reaction that results in the formation of an amide linkage between the carboxyl group of biotin and the epsilon-amino group of the modified lysine . Lipoate-protein ligase A (LPLA) catalyses the formation of an amide linkage between lipoic acid and a specific lysine residue in lipoate dependent enzymes . The unusual biosynthesis pathway of lipoic acid is mechanistically intertwined with attachment of the cofactor .
Wilson KP, Shewchuk LM, Brennan RG, Otsuka AJ, Matthews BW; , Proc Natl Acad Sci USA 1992;89:9257-9261.: Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains. PUBMED:1409631 EPMC:1409631
Chapman-Smith A, Cronan JE Jr; , Trends Biochem Sci 1999;24:359-363.: The enzymatic biotinylation of proteins: a post-translational modification of exceptional specificity. PUBMED:10470036 EPMC:10470036
Morris TW, Reed KE, Cronan JE Jr; , J Biol Chem 1994;269:16091-16100.: Identification of the gene encoding lipoate-protein ligase A of Escherichia coli. Molecular cloning and characterization of the lplA gene and gene product. PUBMED:8206909 EPMC:8206909
Internal database links
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR004143
Biotin and lipoic acid are the covalently bound cofactors of various multicomponent enzyme complexes that catalyze key metabolic reactions. In these enzymes complexes, biotin and lipoic acid are attached via amide linkage through their carboxyl group and the epsilon-amino group of a specific lysine residue of a protein module known respectively as the biotinyl and the lipoyl domain. Covalent attachment of biotin and lipoic acid to these enzyme complexes occurs post-translationally, and it is mediated by biotinylating and lipoylating protein enzymes, which specifically recognise the biotinyl and lipoyl domains, ensuring their correct post-translational modification. Lipoylating and biotinylating enzymes are evolutionarily related protein families containing a homologous catalytic module [ PUBMED:11106165 ].
Amino acid sequence conservation between the catalytic modules of biotinyl protein ligases (BPLs) and lipoyl protein ligases (LPLs) is very low, and mainly affects residues that are important for the scaffold of the structure, such as those contributing to the hydrophobic core. Despite the poor overall sequence similarity, a single lysine residue is strictly conserved in all LPL and BPL sequences. This lysine residue is likely to bind specifically to the carbonyl oxygen of the carboxyl group of biotin or at the end of the hydrogen- carbon tail of the lipoyl moiety [ PUBMED:11106165 ]. The BPL/LPL catalytic domain contains a seven-stranded mixed beta-sheet on one side and four alpha-helices on the other side [ PUBMED:16169557 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Biological process||cellular protein modification process (GO:0006464)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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Aminoacyl-tRNA synthetases are key components of the protein translation machinery that catalyse two basic reactions. First, the activation of amino acids via the formation of aminoacyl adenylates and second, linking the activated amino acid to the cognate tRNAs. The aminoacyl-tRNA synthetases generate AMP as the second end product of this reaction, which differentiates them from the majority of ATP-dependent enzymes that produce ADP. In addition, there is a specific aminoacyl-tRNA synthetases for each of the 20 amino acids and there are two structurally distinct classes of aminoacyl-tRNA synthetases, each encompassing 10 different specificities. The two classes have alternative modes of aminoacylation: class I aminoacylate the 2'OH of the cognate tRNA; class II aminoacylate 3'OH (with the exception of PheRS). Each class contain a conserved core domain that is involved in ATP binding and hydrolysis and combines with additional domains that determine the specificity of interactions with the cognate amino acid and tRNA. The class II core domain consist of a mixed-beta sheet, similar to that found in the biotin synthetases, hence why this family has also been included in this clan. The core domain contains three modestly conserved motifs that are responsible for ATP binding. The class II aminoacyl-tRNA synthetases can contain additional nested domains, found inserted in the loops of the core domain  (and reference therein).
The clan contains the following 11 members:AsnA BPL_LplA_LipB BPL_LplA_LipB_2 DUF366 tRNA-synt_2 tRNA-synt_2b tRNA-synt_2c tRNA-synt_2d tRNA-synt_2e tRNA-synt_His tRNA_synthFbeta
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Seed source:||Reche P|
|Author:||Bateman A , Reche P , Eberhardt R|
|Number in seed:||17|
|Number in full:||15369|
|Average length of the domain:||125.10 aa|
|Average identity of full alignment:||21 %|
|Average coverage of the sequence by the domain:||37.71 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||22|
|Download:||download the raw HMM for this family|
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This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
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Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
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Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
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The tree shows the occurrence of this domain across different species. More...
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the BPL_LplA_LipB domain has been found. There are 144 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.