PROSITE documentation PDOC001682-oxo acid dehydrogenases acyltransferase component lipoyl binding site
The 2-oxo acid dehydrogenase multienzyme complexes [1,2] from bacterial and eukaryotic sources catalyze the oxidative decarboxylation of 2-oxo acids to the corresponding acyl-CoA. The three members of this family of multienzyme complexes are:
- Pyruvate dehydrogenase complex (PDC).
- 2-oxoglutarate dehydrogenase complex (OGDC).
- Branched-chain 2-oxo acid dehydrogenase complex (BCOADC).
These three complexes share a common architecture: they are composed of multiple copies of three component enzymes - E1, E2 and E3. E1 is a thiamine pyrophosphate-dependent 2-oxo acid dehydrogenase, E2 a dihydrolipamide acyltransferase, and E3 an FAD-containing dihydrolipamide dehydrogenase.
E2 acyltransferases have an essential cofactor, lipoic acid, which is covalently bound via a amide linkage to a lysine group. The E2 components of OGCD and BCOACD bind a single lipoyl group, while those of PDC bind either one (in yeast and in Bacillus), two (in mammals), or three (in Azotobacter and in Escherichia coli) lipoyl groups [3].
In addition to the E2 components of the three enzymatic complexes described above, a lipoic acid cofactor is also found in the following proteins:
- H-protein of the glycine cleavage system (GCS) [4]. GCS is a multienzyme complex of four protein components, which catalyzes the degradation of glycine. H protein shuttles the methylamine group of glycine from the P protein to the T protein. H-protein from either prokaryotes or eukaryotes binds a single lipoic group.
- Mammalian and yeast pyruvate dehydrogenase complexes differ from that of other sources, in that they contain, in small amounts, a protein of unknown function - designated protein X or component X. Its sequence is closely related to that of E2 subunits and seems to bind a lipoic group [5].
- Fast migrating protein (FMP) (gene acoC) from Alcaligenes eutrophus [6]. This protein is most probably a dihydrolipamide acyltransferase involved in acetoin metabolism.
We developed a signature pattern which allows the detection of the lipoyl-binding site.
Note:The domain around the lipoyl-binding lysine residue is evolutionary related to that around the biotin-binding lysine residue of biotin requiring enzymes (see <PDOC00167>).
Last update:April 2006 / Pattern revised.
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PURL: https://purl.expasy.org/prosite/documentation/PDOC00168
PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Yeaman S.J. |
| Title | The 2-oxo acid dehydrogenase complexes: recent advances. | |
| Source | Biochem. J. 257:625-632(1989). | |
| PubMed ID | 2649080 |
| 2 | Authors | Yeaman S.J. |
| Source | Trends Biochem. Sci. 11:293-296(1986). |
| 3 | Authors | Russel G.C. Guest J.R. |
| Source | Biochim. Biophys. Acta 1076:225-232(1991). |
| 4 | Authors | Fujiwara K. Okamura-Ikeda K. Motokawa Y. |
| Title | Chicken liver H-protein, a component of the glycine cleavage system. Amino acid sequence and identification of the N epsilon-lipoyllysine residue. | |
| Source | J. Biol. Chem. 261:8836-8841(1986). | |
| PubMed ID | 3522581 |
| 5 | Authors | Behal R.H. Browning K.S. Hall T.B. Reed L.J. |
| Title | Cloning and nucleotide sequence of the gene for protein X from Saccharomyces cerevisiae. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 86:8732-8736(1989). | |
| PubMed ID | 2682658 |
| 6 | Authors | Priefert H. Hein S. Kruger N. Zeh K. Schmidt B. Steinbuechel A. |
| Title | Identification and molecular characterization of the Alcaligenes eutrophus H16 aco operon genes involved in acetoin catabolism. | |
| Source | J. Bacteriol. 173:4056-4071(1991). | |
| PubMed ID | 2061286 |
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