Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.4.1.2 (acetyl-CoA carboxylase)
 2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Definitive evidence is presented for the bifunctional nature of the biotin repressor protein which possesses both regulatory and enzymatic activities. The repressor protein can activate biotin in the presence of ATP to form biotinyl-5'-adenylate, the co-repressor which remains tightly bound to the repressor protein. This complex can either bind to the operator site and inhibit transcription or transfer the biotinyl moiety to a lysine residue of the apoenzyme of acetyl-CoA carboxylase. The two activities were coincident throughout a purification procedure which resulted in a 3500-fold increase in activity. Gel electrophoresis of the purified preparation, under native or denaturing conditions, showed three proteins with the activity corresponding to the major protein band of apparent Mr = 34,000. On gel exclusion chromatography, the activity was also associated with a protein of Mr varying fro 37,000-44,000, indicating the protein is monomeric. The occasional appearance of multiple bands with biological activity in the native gels suggests that the repressor protein can also exist in multimeric forms. On chromatofocusing, the repressor activity and the holoenzyme synthetase activity were coincidental, with the peak of activity at pH 7.2, the isoelectric point. Only a single protein band with Mr = 34,000 was observed on SDS gel electrophoresis of all fractions showing activity.
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PMID:Purification and properties of the biotin repressor. A bifunctional protein. 612 46

Transcription of the biotin (bio) biosynthetic operon of Escherichia coli is negatively regulated by the BirA protein, an atypical repressor protein in that it is also an enzyme. The BirA-catalyzed reaction involves the covalent attachment of biotin to AccB, a subunit of acetyl coenzyme (acetyl-CoA) carboxylase. The two functions of BirA allow regulation of the bio operon to respond to the intracellular concentrations of both biotin and unbiotinylated AccB. We report here that bio operon expression is down-regulated by overproduction of AccC, another acetyl-CoA carboxylase subunit known to form a complex with AccB. This down-regulation is eliminated when AccB and AccC are coordinately overexpressed, but only when the AccB partner is competent to bind AccC. Under AccC overexpression conditions AccB is underbiotinylated. These findings can be explained by a model in which excess AccC sequesters AccB in a complex that is a poor substrate for biotinylation. The observed disruption of biotin synthesis and attachment provides an excellent rationale for the observation that in the vast majority of sequenced bacterial genomes AccB and AccC are encoded in a two-gene operon.
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PMID:Coordinate expression of the acetyl coenzyme A carboxylase genes, accB and accC, is necessary for normal regulation of biotin synthesis in Escherichia coli. 1705 47