Lipoamide Acyltransferase (IPR015761)
Short name: BCKDC_E2
This entry represents the mitochondrial lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex (also known as component E2). It belongs to the 2-oxoacid dehydrogenase family. The branched-chain alpha-keto dehydrogenase complex catalyses the overall conversion of alpha-keto acids to acyl-CoA and CO2. Within this complex, the catalytic function of this enzyme is to accept, and to transfer to coenzyme A, acyl groups that are generated by the branched-chain alpha-keto acid decarboxylase component [PMID: 11917081, PMID: 17124494].
The 2-oxo acid dehydrogenase multienzyme complexes [PMID: 2649080] from bacterial and eukaryotic sources include:
- Pyruvate dehydrogenase complex (PDC);
- 2-oxoglutarate dehydrogenase complex (OGDC);
- Branched-chain alpha-ketoacid dehydrogenase complex (BCKDC).
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 is an FAD-containing dihydrolipamide dehydrogenase.
E2 acyltransferases have an essential cofactor, lipoic acid, which is covalently bound via an amide linkage to a lysine group. The E2 components of OGCD and BCKDC 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 [PMID: 1825611].
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) [PMID: 3522581]. 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 [PMID: 2682658];
- Fast migrating protein (FMP) (gene acoC) from Ralstonia eutropha (Alcaligenes eutrophus) [PMID: 2061286]. This protein is most probably a dihydrolipamide acyltransferase involved in acetoin metabolism.
- PTHR23151:SF71 (PTHR23151:SF71)