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)

Biotin carboxyl carrier protein (BCCP) is the small biotinylated subunit of Escherichia coli acetyl-CoA carboxylase, the enzyme that catalyzes the first committed step of fatty acid synthesis. E. coli BCCP is a member of a large family of protein domains modified by covalent attachment of biotin. In most biotinylated proteins, the biotin moiety is attached to a lysine residue located about 35 residues from the carboxyl terminus of the protein, which lies in the center of a strongly conserved sequence that forms a tightly folded anti-parallel beta-barrel structure. Located upstream of the conserved biotinoyl domain sequence are proline/alanine-rich sequences of varying lengths, which have been proposed to act as flexible linkers. In E. coli BCCP, this putative linker extends for about 42 residues with over half of the residues being proline or alanine. I report that deletion of the 30 linker residues located adjacent to the biotinoyl domain resulted in a BCCP species that was defective in function in vivo, although it was efficiently biotinylated. Expression of this BCCP species failed to restore normal growth and fatty acid synthesis to a temperature-sensitive E. coli strain that lacks BCCP when grown at nonpermissive temperatures. In contrast, replacement of the deleted BCCP linker with a linker derived from E. coli pyruvate dehydrogenase gave a chimeric BCCP species that had normal in vivo function. Expression of BCCPs having deletions of various segments of the linker region of the chimeric protein showed that some deletions of up to 24 residues had significant or full biological activity, whereas others had very weak or no activity. The inactive deletion proteins all lacked an APAAAAA sequence located adjacent to the tightly folded biotinyl domain, whereas deletions that removed only upstream linker sequences remained active. Deletions within the linker of the wild type BCCP protein also showed that the residues adjacent to the tightly folded domain play an essential role in protein function, although in this case some proteins with deletions within this region retained activity. Retention of activity was due to fusion of the domain to upstream sequences. These data provide new evidence for the functional and structural similarities of biotinylated and lipoylated proteins and strongly support a common evolutionary origin of these enzyme subunits.
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PMID:Interchangeable enzyme modules. Functional replacement of the essential linker of the biotinylated subunit of acetyl-CoA carboxylase with a linker from the lipoylated subunit of pyruvate dehydrogenase. 1195 2

Acetyl-CoA carboxylase (ACC) catalyzes the first step of fatty acid biosynthesis, the synthesis of malonyl-CoA from acetyl-CoA using ATP and bicarbonate. In Escherichia coli and most other bacteria, ACC is composed of four subunits encoded by accA, accB, accC, and accD. Prior work from this laboratory showed that the in vivo expression of the accBC operon had a strikingly nonlinear response to gene copy number (Li, S.-J, and Cronan, J. E., Jr. (1993) J. Bacteriol. 175, 332-340) in that the presence of 50 or more copies of the accBC operon resulted in only a 2-3-fold increase in AccB and AccC. We now report that AccB functions to negatively regulate transcription of the accBC operon. Expression of a chimeric protein consisting of the N terminus of E. coli AccB and the C-terminal bioinylation domain of Bacillus subtilis AccB down-regulated transcription of the E. coli accBC operon. A truncated form of AccB consisting of the N-terminal 68 amino acids of E. coli AccB was sufficient to negatively regulate the accBC operon. In vivo bypass of acetyl-CoA carboxylase activity by expression of a malonyl-CoA synthase from Rhizobium trifolii allowed construction of strain deleted for the accA and accB genes. Unexpectedly, the deltaaccB mutation could not be resolved from the deltaaccA mutation. Transcription of the accBC operon in the deltaaccB deltaaccA strain continued well into stationary phase under growth conditions that normally result in greatly decreased transcription. These data support a model in which AccB acts as an autoregulator of accBC operon transcription.
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PMID:Expression of two Escherichia coli acetyl-CoA carboxylase subunits is autoregulated. 1459 96