Biochemical and structural characterization of an essential acyl coenzyme a carboxylase from Mycobacterium tuberculosis
In: Journal of Bacteriology, Jg. 188 (2006), Heft 1-2, S. 477-486
academicJournal
Zugriff:
Pathogenic mycobacteria contain a variety of unique fatty acids that have methyl branches at an even-numbered position at the carboxyl end and a long n-aliphatic chain. One such group of acids, called mycocerosic acids, is found uniquely in the cell wall of pathogenic mycobacteria, and their biosynthesis is essential for growth and pathogenesis. Therefore, the biosynthetic pathway of the unique precursor of such lipids, methylmalonyl coenzyme A (CoA), represents an attractive target for developing new antituberculous drugs. Heterologous protein expression and purification of the individual subunits allowed the successful reconstitution of an essential acyl-CoA carboxylase from Mycobacterium tuberculosis, whose main role appears to be the synthesis of methylmalonyi-CoA. The enzyme complex was reconstituted from the [alpha] biotinylated subunit AccA3, the carboxyitransferase [beta] subunit AccD5, and the e subunit AccD5 (Rv3281). The kinetic properties of this enzyme showed a clear substrate preference for propionyl-CoA compared with acetyl-CoA (specificity constant fivefold higher), indicating that the main physiological role of this enzyme complex is to generate methyimalonyl-CoA for the biosynthesis of branched-chain fatty acids. The [alpha] and [beta] subunits are capable of forming a stable [alpha]6-[beta]6 subcomplex but with very low specific activity. The addition of the [epsilon] subunit, which binds tightly to the [alpha]-[beta] subcomplex, is essential for gaining maximal enzyme activity.
Titel: |
Biochemical and structural characterization of an essential acyl coenzyme a carboxylase from Mycobacterium tuberculosis
|
---|---|
Autor/in / Beteiligte Person: | Gago, Gabriela ; Kurth, Daniel ; Diacovich, Lautaro ; Tsai, Shiou-Chuan ; Gramajo, Hugo |
Zeitschrift: | Journal of Bacteriology, Jg. 188 (2006), Heft 1-2, S. 477-486 |
Veröffentlichung: | 2006 |
Medientyp: | academicJournal |
ISSN: | 0021-9193 (print) |
Schlagwort: |
|
Sonstiges: |
|