InterPro domain: IPR004408

The biotin operon of Escherichia coli contains 5 structural genes involved in the synthesis of biotin. Transcription of the operon is regulated via one of these proteins, the biotin ligase BirA. BirA is an asymetric protein with 3 specific domains - an N-terminal DNA-binding domain, a central catalytic domain and a C-terminal of unknown function. The ligase reaction intermediate, biotinyl-5'-AMP, is the co-repressor that triggers DNA binding by BirA.The alpha-helical N-terminal domain of the BirA protein has the helix-turn-helix structure of DNA-binding proteins with a central DNA recognition helix. BirA undergoes several conformational changes related to repressor function and the N-terminal DNA-binding function is connected to the rest of the molecule through a hinge which will allow relocation of the domains during the reaction [ 1 ]. Biotin-binding causes a large structural change thought to facilitate ATP-binding.

Two repressor molecules form the operator-repressor complex, with dimer formation occuring simultaneously with DNA binding. DNA-binding may also cause a conformational change which allows this co-operative interaction. In the dimer structure, the beta-sheets in the central domain of each monomer are arranged side-by-side to form a single, seamless beta-sheet.

The apparent orthologs among the eukaryotes are larger proteins that contain a domain with high sequence homology to BirA.

1. The enzymatic biotinylation of proteins: a post-translational modification of exceptional specificity. Trends Biochem. Sci. 24, 359-63