INVESTIGADORES
GAGO Gabriela Marisa
congresos y reuniones científicas
Título:
Structural study of the transcriptional regulators MabR and FasR from Mycobacterium tuberculosis: control of fatty acid biosynthesis and lipid homeostasis.
Autor/es:
LARA, J; DIACOVICH, L.; LARRIEUX, N; BUSCHIAZZO, A; GAGO, G.; GRAMAJO, H
Lugar:
Córdoba
Reunión:
Congreso; IX Reunión Anual de la Asociación Argentina de Cristalografía (AACr) y I Reunión Latinoamericana de Cristalografía; 2013
Institución organizadora:
AACr
Resumen:
STRUCTURAL STUDY OF THE TRANSCRIPTIONAL REGULATORS MabR
AND FasR FROM Mycobacterium tuberculosis: CONTROLOF FATTY ACID
BIOSYNTHESIS AND LIPID HOMEOSTASIS
Lara Julia1, Diacovich Lautaro1, Larrieux Nicole2, Buschiazzo Alejandro2, Gago Gabriela1,
and Gramajo Hugo1
1 Instituto de Biología Molecular y Celular de Rosario. IBR-CONICET, Rosario-Argentina. 2 Institut Pasteur de
Montevideo. IP Montevideo, Montevideo-Uruguay. E-mail: lara@ibr-conicet.gov.ar
Mycolic acids (MA) present at the cell wall of M. tuberculosis play an important role in its architecture,
impermeability and antibiotic exclusion of this human pathogen. Mycobacteria, unlike most bacteria, have two fatty acid
synthases (FAS-I and FAS-II) [1] which work in concert to synthetize MA. Our research group identified two
transcriptional regulators essential for mycobacterial viability, involved in the regulatory network of fatty acids
biosynthesis. MabR, which controls the expression of fasII operon genes by binding to the fasII promoter region, and
FasR, which specifically binds to fas promoter region and controls the de novo fatty acid biosynthesis [2,3].In order to
deeply characterize the molecular bases of MabR and FasR interaction with their corresponding DNA targets, we
performed experiments to obtain the crystal structures of both transcriptional regulators. Both proteins were screened
based on sitting drop vapor diffusion. Laminar crystals of His-MabR were obtained, although not suitable for structural
determination. Then, we explored new crystallization conditions using the native protein (without His6-tag) and found rodlike
crystals in the presence of the DNA interacting probe. Additionally, we recently established conditions where small
crystals of FasR native protein were obtained. Currently, we are optimizing the crystallization conditions for both proteins
in order to obtain diffraction data. The structural characterization of these novel transcriptional regulators might provide
significant information for the development of conceptually new antimycobacterium compounds.