title: Lipoylating and biotinylating enzymes contain a homologous catalytic module.
abstract: Biotin and lipoic acid moieties are the covalently attached coenzyme cofactors of several multicomponent enzyme complexes that catalyze key metabolic reactions. Attachment of these moieties to the biotinyl- and lipoyl-dependent enzymes is post-translationally catalyzed by specific biotinylating and lipoylating protein enzymes. In Escherichia coli, two different enzymes, LplA and LipB, catalyze independent pathways for the lipoylation of the relevant enzymes, whereas only one enzyme, the BirA protein, is responsible for all the biotinylation. Counterparts of the E. coli BirA, LplA, and LipB enzymes have been previously identified in many organisms, but homology among the three families has never been reported. Computational analysis based on PSI-BLAST profiles and secondary structure predictions indicates, however, that lipoylating and biotinylating enzymes are evolutionarily related protein families containing a homologous catalytic module. Sequence conservation among the three families is very poor, but a single lysine residue is strictly conserved in all of them, which, according to the available X-ray crystal structure of the E. coli BirA protein, is expected to contribute to the binding of lipoic acid in the LplA and LipB enzymes.
authors: DNAX Research Institute, Department of Molecular Biology, Palo Alto, California 94304-1104, USA. reche@dnax.org
authors: P A
authors: PA
authors: Reche
mesh_terms: D000217:Acyltransferases; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001710:Biotin / Q000378:metabolism; D019921:Biotinylation; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins; D019143:Evolution, Molecular; D008025:Ligases; D008074:Lipoproteins / Q000737:chemistry* / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D008063:Thioctic Acid / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008074:Lipoproteins; D008565:Membrane Proteins; D011506:Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C490345:lplA protein, E coli; C089935:lplA protein, bacteria; D001710:Biotin; D008063:Thioctic Acid; D000217:Acyltransferases; C421483:LipB protein, E coli; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C058125:birA protein, E coli