Disease relevance of aidB

• Structure and transcriptional regulation of the Escherichia coli adaptive response gene aidB [1].
• The aidB gene is not expressed constitutively, but its transcription is induced via distinct mechanisms in response to: (i) exposure to alkylating agents; (ii) acetate at a slightly acidic pH; and (iii) anoxia [2].

High impact information on aidB

• The growth phase-dependent control of the aidB fusions, however, is unaffected by ada, suggesting that a second regulatory mechanism exists that controls only aidB [3].
• Thus, both aidA and aidB share with adaptive response a common regulatory mechanism involving the ada gene [3].
• The other region (aidB) is in the 92.3- to 98-min region, which harbors no previously identified genes involved in repair of alkylation damage [3].
• Isovaleric acidemia is a rare inborn error of metabolism caused by a deficiency of isovaleryl-CoA dehydrogenase (IVD), a nucleus-encoded, homotetrameric, mitochondrial flavoenzyme that catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA [4].
• Unmethylated Ada protein shows no protection against DNaseI digestion in the aidB promoter region nor does it promote aidB in vitro transcription [5].

Biological context of aidB

• Ada protein plays a direct role in aidB regulation: methylated Ada is able to bind to the aidB promoter region and to activate transcription from aidB in an in vitro transcription-translation system using crude E. coli extracts [1].
• Accordingly, crude extracts from an aidB-overexpressing strain showed isovaleryl coenzyme A dehydrogenase activity. aidB overexpression also reduced N-methyl-N'-nitro-N-nitrosoguanidine-induced mutagenesis [1].
• Expression of the Escherichia coli aidB gene is induced in vivo by alkylation damage in an ada-dependent pathway and by anaerobiosis or by acetate at pH 6.5 in an ada-independent fashion [1].
• Transcriptional activation of the Escherichia coli adaptive response gene aidB is mediated by binding of methylated Ada protein. Evidence for a new consensus sequence for Ada-binding sites [5].
• Through DNaseI protection assays, we show that methylated Ada (meAda) is able to bind a DNA sequence between 40 and 60 base pairs upstream of the aidB transcriptional startpoint [5].

Associations of aidB with chemical compounds

• The aidB gene encodes a protein of ca. 60 kDa that is homologous to several mammalian acyl coenzyme A dehydrogenases [1].
• However, sigma s-dependent transcription of aidB is inhibited both in vitro and in vivo by binding of the transcriptional regulator Lrp (leucine responsive protein) to the aidB promoter region (PaidB) [2].
• However, the alanine substitutions of positively charged residues K593, K597, and R603 do not affect meAda-dependent transcription at ada and aidB [6].
• We show that although Esigma(70) can bind the aidB promoter, its interaction with the promoter results in the formation of an open complex inefficient in transcription initiation and sensitive to heparin challenge [7].

References