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PROSITE documentation PDOC00168 [for PROSITE entry PS00189]

2-oxo acid dehydrogenases acyltransferase component lipoyl binding site





Description

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.

Technical section

PROSITE method (with tools and information) covered by this documentation:

LIPOYL, PS00189; 2-oxo acid dehydrogenases acyltransferase component lipoyl binding site  (PATTERN)


References

1AuthorsYeaman S.J.
TitleThe 2-oxo acid dehydrogenase complexes: recent advances.
SourceBiochem. J. 257:625-632(1989).
PubMed ID2649080

2AuthorsYeaman S.J.
SourceTrends Biochem. Sci. 11:293-296(1986).

3AuthorsRussel G.C., Guest J.R.
SourceBiochim. Biophys. Acta 1076:225-232(1991).

4AuthorsFujiwara K., Okamura-Ikeda K., Motokawa Y.
TitleChicken liver H-protein, a component of the glycine cleavage system. Amino acid sequence and identification of the N epsilon-lipoyllysine residue.
SourceJ. Biol. Chem. 261:8836-8841(1986).
PubMed ID3522581

5AuthorsBehal R.H., Browning K.S., Hall T.B., Reed L.J.
TitleCloning and nucleotide sequence of the gene for protein X from Saccharomyces cerevisiae.
SourceProc. Natl. Acad. Sci. U.S.A. 86:8732-8736(1989).
PubMed ID2682658

6AuthorsPriefert H., Hein S., Kruger N., Zeh K., Schmidt B., Steinbuechel A.
TitleIdentification and molecular characterization of the Alcaligenes eutrophus H16 aco operon genes involved in acetoin catabolism.
SourceJ. Bacteriol. 173:4056-4071(1991).
PubMed ID2061286



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