Cofactor transferase family

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Cofactor transferase domain
PDB 1bia EBI.jpg
The three-dimensional structure of BirA, the repressor of the Escherichia coli biotin biosynthetic operon. [1]
Identifiers
SymbolBPL
Pfam PF03099
InterPro IPR004143
SCOP2 1bia / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Bacterial lipoate protein ligase C-terminus
PDB 1vqz EBI.jpg
crystal structure of putative lipoate-protein ligase (np_345629.1) from streptococcus pneumoniae tigr4 at 1.99 a resolution
Identifiers
SymbolLip_prot_lig_C
Pfam PF10437
InterPro IPR019491
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Biotin protein ligase C terminal domain
Identifiers
SymbolBPL_C
Pfam PF02237
Pfam clan CL0206
InterPro IPR003142
SCOP2 1bia / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

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. [2] 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. [3]

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. [4]

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. [5] Two octanoyltransferase isozymes exist in this superfamily. [6]

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. [7] [8]

Structure

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. [1] [2]

Related Research Articles

<span class="mw-page-title-main">Lipoic acid</span> Chemical compound

Lipoic acid (LA), also known as α-lipoic acid, alpha-lipoic acid (ALA) and thioctic acid, is an organosulfur compound derived from caprylic acid (octanoic acid). ALA is made in animals normally, and is essential for aerobic metabolism. It is also manufactured and is available as a dietary supplement in some countries where it is marketed as an antioxidant, and is available as a pharmaceutical drug in other countries. Lipoate is the conjugate base of lipoic acid, and the most prevalent form of LA under physiological conditions. Only the (R)-(+)-enantiomer (RLA) exists in nature and is essential for aerobic metabolism because RLA is an essential cofactor of many enzyme complexes.

<span class="mw-page-title-main">Acetyl-CoA carboxylase</span> Enzyme that regulates the metabolism of fatty acids

Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase (BC) and carboxyltransferase (CT). ACC is a multi-subunit enzyme in most prokaryotes and in the chloroplasts of most plants and algae, whereas it is a large, multi-domain enzyme in the cytoplasm of most eukaryotes. The most important function of ACC is to provide the malonyl-CoA substrate for the biosynthesis of fatty acids. The activity of ACC can be controlled at the transcriptional level as well as by small molecule modulators and covalent modification. The human genome contains the genes for two different ACCs—ACACA and ACACB.

<span class="mw-page-title-main">Aspartate kinase</span> Class of enzymes

Aspartate kinase or aspartokinase (AK) is an enzyme that catalyzes the phosphorylation of the amino acid aspartate. This reaction is the first step in the biosynthesis of three other amino acids: methionine, lysine, and threonine, known as the "aspartate family". Aspartokinases are present only in microorganisms and plants, but not in animals, which must obtain aspartate-family amino acids from their diet. Consequently, methionine, lysine and threonine are essential amino acids in animals.

Lipoyl synthase is an enzyme that belongs to the radical SAM (S-adenosyl methionine) family. Within the radical SAM superfamily, lipoyl synthase is in a sub-family of enzymes that catalyze sulfur insertion reactions. Enzymes in this family contain two 4Fe-4S clusters, from which they obtain the sulfur groups that will be transferred onto the corresponding substrates. This particular enzyme participates in lipoic acid metabolism, so it transfers two sulfur atoms from its 4Fe-4S cluster onto the protein N6-(octanoyl)lysine through radical generation. This enzyme is usually localized to the mitochondria. Two organisms that have been extensively studied with regards to this enzyme are Escherichia coli and Mycobacterium tuberculosis. It is also found in other organisms, such as yeast and plants.

<span class="mw-page-title-main">Diaminopimelate decarboxylase</span>

The enzyme diaminopimelate decarboxylase (EC 4.1.1.20) catalyzes the cleavage of carbon-carbon bonds in meso 2,6 diaminoheptanedioate to produce CO2 and L-lysine, the essential amino acid. It employs the cofactor pyridoxal phosphate, also known as PLP, which participates in numerous enzymatic transamination, decarboxylation and deamination reactions.

<span class="mw-page-title-main">Biotin carboxylase</span> Class of enzymes

In enzymology, a biotin carboxylase (EC 6.3.4.14) is an enzyme that catalyzes the chemical reaction

In enzymology, a long-chain-fatty-acid—[acyl-carrier-protein] ligase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Phosphoribosylamine—glycine ligase</span>

Phosphoribosylamine—glycine ligase, also known as glycinamide ribonucleotide synthetase (GARS), (EC 6.3.4.13) is an enzyme that catalyzes the chemical reaction

In enzymology, a [acyl-carrier-protein] S-malonyltransferase is an enzyme that catalyzes the chemical reaction

In enzymology, a beta-ketoacyl-acyl-carrier-protein synthase I is an enzyme that catalyzes the chemical reaction

In enzymology, a lipoyl(octanoyl) transferase (EC 2.3.1.181) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Holo-(acyl-carrier-protein) synthase</span>

In enzymology and molecular biology, a holo-[acyl-carrier-protein] synthase is an enzyme that catalyzes the chemical reaction:

Biotin/lipoyl attachment domain has a conserved lysine residue that binds biotin or lipoic acid. Biotin plays a catalytic role in some carboxyl transfer reactions and is covalently attached, via an amide bond, to a lysine residue in enzymes requiring this coenzyme. Lipoamide acyltransferases have an essential cofactor, lipoic acid, which is covalently bound via an amide linkage to a lysine group. The lipoic acid cofactor is found in a variety of proteins.

<span class="mw-page-title-main">Fatty acid metabolism regulator protein FadR</span>

In molecular biology, the fatty acid metabolism regulator protein FadR, is a bacterial transcription factor.

Radical SAM is a designation for a superfamily of enzymes that use a [4Fe-4S]+ cluster to reductively cleave S-adenosyl-L-methionine (SAM) to generate a radical, usually a 5′-deoxyadenosyl radical (5'-dAdo), as a critical intermediate. These enzymes utilize this radical intermediate to perform diverse transformations, often to functionalize unactivated C-H bonds. Radical SAM enzymes are involved in cofactor biosynthesis, enzyme activation, peptide modification, post-transcriptional and post-translational modifications, metalloprotein cluster formation, tRNA modification, lipid metabolism, biosynthesis of antibiotics and natural products etc. The vast majority of known radical SAM enzymes belong to the radical SAM superfamily, and have a cysteine-rich motif that matches or resembles CxxxCxxC. rSAMs comprise the largest superfamily of metal-containing enzymes.

Lipoyl amidotransferase (EC 2.3.1.200, LipL (gene)) is an enzyme with systematic name (glycine cleavage system H)-N6-lipoyl-L-lysine:(lipoyl-carrier protein)-N6-L-lysine lipoyltransferase. This enzyme catalyses the following chemical reaction

Octanoyl-(GcvH):protein N-octanoyltransferase (EC 2.3.1.204, LIPL, octanoyl-[GcvH]:E2 amidotransferase, YWFL (gene)) is an enzyme with systematic name (glycine cleavage system H)-N6-octanoyl-L-lysine:(lipoyl-carrier protein)-N6-L-lysine octanoyltransferase. This enzyme catalyses the following chemical reaction

Lipoate–protein ligase (EC 2.7.7.63, LplA, lipoate protein ligase, lipoate–protein ligase A, LPL, LPL-B) is an enzyme with systematic name ATP:lipoate adenylyltransferase. This enzyme catalyses the following chemical reaction

The enzyme Pimelyl-[acyl-carrier protein] methyl ester esterase (EC 3.1.1.85, BioH; systematic name pimelyl-[acyl-carrier protein] methyl ester hydrolase catalyses the reaction

3-hydroxydecanoyl-(acyl-carrier-protein) dehydratase (EC 4.2.1.60, D-3-hydroxydecanoyl-[acyl-carrier protein] dehydratase, 3-hydroxydecanoyl-acyl carrier protein dehydrase, 3-hydroxydecanoyl-acyl carrier protein dehydratase, β-hydroxydecanoyl thioester dehydrase, β-hydroxydecanoate dehydrase, beta-hydroxydecanoyl thiol ester dehydrase, FabA, β-hydroxyacyl-acyl carrier protein dehydratase, HDDase, β-hydroxyacyl-ACP dehydrase, (3R)-3-hydroxydecanoyl-[acyl-carrier-protein] hydro-lyase) is an enzyme with systematic name (3R)-3-hydroxydecanoyl-(acyl-carrier protein) hydro-lyase. This enzyme catalyses the following chemical reaction

References

  1. 1 2 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): 9257–61. Bibcode:1992PNAS...89.9257W. doi: 10.1073/pnas.89.19.9257 . PMC   50105 . PMID   1409631.
  2. 1 2 Reche PA (October 2000). "Lipoylating and biotinylating enzymes contain a homologous catalytic module". Protein Sci. 9 (10): 1922–9. doi:10.1110/ps.9.10.1922. PMC   2144473 . PMID   11106165.
  3. ↑ Chapman-Smith A, Cronan JE (September 1999). "The enzymatic biotinylation of proteins: a post-translational modification of exceptional specificity". Trends Biochem. Sci. 24 (9): 359–63. doi:10.1016/s0968-0004(99)01438-3. PMID   10470036.
  4. ↑ 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): 16091–100. doi: 10.1016/S0021-9258(17)33977-7 . PMID   8206909.
  5. ↑ Cronan JE, Zhao X, Jiang Y (2005). Function, attachment and synthesis of lipoic acid in Escherichia coli. Adv. Microb. Physiol. Advances in Microbial Physiology. Vol. 50. pp. 103–46. doi:10.1016/S0065-2911(05)50003-1. ISBN   9780120277506. PMID   16221579.
  6. ↑ Christensen QH, Cronan JE (2010). "Lipoic acid synthesis: a new family of octanoyltransferases generally annotated as lipoate protein ligases". Biochemistry. 49 (46): 10024–36. doi:10.1021/bi101215f. PMC   2982868 . PMID   20882995.
  7. ↑ 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): 350–63. doi:10.1111/j.1365-2958.2011.07598.x. PMC   3088481 . PMID   21338421.
  8. ↑ 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): 335–49. doi:10.1111/j.1365-2958.2011.07597.x. PMC   3086205 . PMID   21338420.
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