Repressor BirA

Repressors may have similar recognition domains but may vary greatly both in size and in the functioning of their other domains, which may react both with small allosteric effectors and with other proteins. The repressor BirA of the E. coli biotin synthesis operon is an enzyme. The 321-residue protein activates biotin to form biotinyl 5 -adenylate and transfers the biotinyl group to proteins such as acetyl-CoA carboxylase107-1093 and also represses transcription. 

Numerous studies performed with E. coli have established that, in E. coli, biotin regulates very efficiently its biosynthetic pathway, with an absolute specificity, the biotin vitamers being inactive. As the topics has been largely reviewed, it will be only summarized here. The regulation occurs at the transcriptional level and the biotin operon repressor (BirA) has been well characterized. This 33.5 kDa bifiinctional protein is both an enzyme and a transcriptional regulator (Figure 21). It activates biotin into biotinyl-5 -AMP with ATP (reaction a) and transfers biotin on a specific lysine residue of the biotin accepting proteins (in E. coli, the biotin carboxyl carrier protein (BCCP), a subunit of acetyl-CoA carboxylase) (reaction b). When all the... 

The bio genes so far identified in E. coli are represented in Figure 5. In addition to the biosynthetic genes bioABFCD, which are clustered on a divergent operon that is negatively controlled by the BirA-biotinyl-5 -AMP complex (15,16), there are three other bio genes bioR, which codes for the repressor (BirA protein) that also supports the holocarboxylase synthetase activity (see below) bioH, probably involved in early steps of the biosynthesis (17) and bioP, which codes for the specific carrier for biotin (15,18). The biotin repressor, for which a three-dimensional structure is now available, has both been studied as a model for baeterial DNA repressors and as a model for holocarboxylase synthetases (19,20). 

Several aaRS-like proteins are involved in metabobc pathways (1). For example, E. coli asparagine synthase, an aspartyl-tRNA synthetase (AspRS)-like enzyme, catalyzes the synthesis of asparagine from aspartate and ATP. A paralog of LysRS-II, called PoxA/GenX, is important for pyruvate oxidase activity in E. coli and Salmonella typhimurium and for virulence in S. typhimurium. The E. coli biotin synthetase/repressor protein (BirA), which has a domain that resembles structurally the seryl-tRNA synthetase (SerRS) catalytic domain, activates biotin to modify posttranslationaUy various metabolic proteins involved in carboxylation and decarboxylation. BirA can also bind DNA and regulate its own transcription using biotin as a corepressor. A histidyl-tRNA synthetase (HisRS)-hke protein from Lactococcus lactis, HisZ is involved in the allosteric activation of the phosphoribosyl-transferase reaction. 

Howard, P.K., Shaw, J. and Otsuka, A.J. (1985) Nucleotide sequence of the birA gene encoding the biotin operon repressor and biotin holoenzyme synthetase functions of Escherichia coli. Gene 35, 321-331... 

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