IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
CHARACTERIZATION OF THE LONG-CHAIN ACYL-COA CARBOXYLASE OF Mycobacterium tuberculosis
Autor/es:
BAZET LYONET BERNARDO; DIACOVICH LAUTARO; GAGO GABRIELA; GRAMAJO HUGO
Lugar:
Mar del Plata
Reunión:
Congreso; Reunión Anual Nº 51 (LI) de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2015
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)
Resumen:
The two Fatty Acid Synthase (FAS) systems of the human pathogen Mycobacterium tuberculosis work in concert to synthesize mycolic acids. FAS I builds a long-chain acyl-CoA (C24-CoA) and FAS II generate a very long-chain fatty acid (meromycolic acid). A long-chain acyl-CoA carboxylase (LCC) activates the C24 acyl-CoA, and the acyl-AMP ligase FadD32 activates the meromycolic acid chain. These two chains are later condensed by Pks13 to yield the final mycolic acid. Besides its importance in mycolic acid biosynthesis, there were no conclusive results of the subunit composition of the acyl-CoA carboxylase responsible to generate the long-chain carboxyacyl-CoA. Previous results suggested that the subunits AccA3 and AccD4 were part of this LCC complex. Analysis of an accD5-accE5 conditional mutant in M. smegmatis allowed us to speculate that the subunits AccD5 and AccE5, that are part a of well-characterized propionyl-CoA carboxylase, are also involved in the long-chain acyl-CoA carboxylation. To solve this issue, we developed an in vitro assay for measuring LCC activity in the presence of its purified subunits. By using this assay we demonstrated that the LCC complex is formed the subunits AccA3, AccD4, AccD5 and AccE5. The specific role of AccD5 and AccE5, and the kinetic characterization of this enzyme complex are now under study.