PROSITE documentation PDOC50968
Biotinyl/lipoyl domain profile


Biotin and lipoic acid moieties are the covalently bound cofactors of several multicomponent enzyme complexes that catalyze key metabolic reactions. They are attached to a lysine residue, via an amide bond, by specific biotinyl and lipoyl protein ligases. The lipoyl-lysine and biotinyl-lysine residues serve as swinging arms, ferrying substrate between the three active sites in their relevant enzyme complexes [1]. The 80 residues surrounding the biotinyl-binding lysine residue (see <PDOC00167>) display some sequence similarity to that around the lipoyl-binding lysine residue (see <PDOC00168>).

The lipoyl domains of 2-oxo acid dehydrogenase multienzyme complexes and the biotinyl domains of biotin-dependent enzymes have been solved [2,3] (see for example <PDB:1PMR>). They have homologous structures (a flattened 8-stranded -barrel) with their target lysine residues positioned in comparable β-turns. Several residues important for the specificity have been identified, most notably the conserved methionine flanking the target lysine is essential for the recognition of the biotinyl domain by the biotinyl protein ligase [4].

Enzymes that contain a biotinyl domain are listed below:

  • Pyruvate carboxylase (EC
  • Acetyl-CoA carboxylase (EC
  • Propionyl-CoA carboxylase (EC
  • Methylcrotonyl-CoA carboxylase (EC
  • Geranoyl-CoA carboxylase (EC
  • Urea carboxylase (EC
  • Oxaloacetate decarboxylase (EC
  • Methylmalonyl-CoA decarboxylase (EC
  • Glutaconyl-CoA decarboxylase (EC
  • Methylmalonyl-CoA carboxyl-transferase (EC (transcarboxylase).

Enzymes that contain a lipoyl domain are listed below:

  • Pyruvate dehydrogenase complex (PDC).
  • 2-oxoglutarate dehydrogenase complex (OGDC).
  • Branched-chain 2-oxo acid dehydrogenase complex (BCOADC).
  • Glycine cleavage system H protein (GCSH) [5].

The profile we developed covers the whole biotinyl/lipoyl domain.

Last update:

September 2014 / Profile and text revised.


Technical section

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

BIOTINYL_LIPOYL, PS50968; Biotinyl/lipoyl domain profile  (MATRIX)


1AuthorsPerham R.N. Reche P.A.
TitleSwinging arms in multifunctional enzymes and the specificity of post-translational modification.
SourceBiochem. Soc. Trans. 26:299-303(1998).
PubMed ID9765868

2AuthorsRicaud P.M. Howard M.J. Roberts E.L. Broadhurst R.W. Perham R.N.
TitleThree-dimensional structure of the lipoyl domain from the dihydrolipoyl succinyltransferase component of the 2-oxoglutarate dehydrogenase multienzyme complex of Escherichia coli.
SourceJ. Mol. Biol. 264:179-190(1996).
PubMed ID8950276

3AuthorsAthappilly F.K. Hendrickson W.A.
TitleStructure of the biotinyl domain of acetyl-coenzyme A carboxylase determined by MAD phasing.
SourceStructure 3:1407-1419(1995).
PubMed ID8747466

4AuthorsReche P.A. Howard M.J. Broadhurst R.W. Perham R.N.
TitleHeteronuclear NMR studies of the specificity of the post-translational modification of biotinyl domains by biotinyl protein ligase.
SourceFEBS Lett. 479:93-98(2000).
PubMed ID10981714

5AuthorsReche P. Perham R.N.
TitleStructure and selectivity in post-translational modification: attaching the biotinyl-lysine and lipoyl-lysine swinging arms in multifunctional enzymes.
SourceEMBO J. 18:2673-2682(1999).
PubMed ID10329614

PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)