Lipoylating and biotinylating enzymes contain a homologous catalytic module

Biotin and lipoic acid moieties are the covalently attached coenzyme cofact ors of several multicomponent enzyme complexes that catalyze key metabolic reactions. Attachment of these moieties to the biotinyl- and lipoyl-depende nt enzymes is post-translationally catalyzed by specific biotinylating and lipoylating protein enzymes. In Escherichia coli, two different enzymes, Lp lA and LipB, catalyze independent pathways for the lipoylation of the relev ant enzymes, whereas only one enzyme, the BirA protein, is responsible for all the biotinylation. Counterparts of the E. coli BirA, LplA, and LipB enz ymes 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 prot ein families containing a homologous catalytic module. Sequence conservatio n among the three families is very poor, but a single lysine residue is str ictly conserved in all of them, which, according to the available X-ray cry stal structure of the E. coli BirA protein, is expected to contribute to th e binding of lipoic acid in the LplA and LipB enzymes.