![The elucidation of the structure of the PaaX repressor allows a better understanding of the regulation of phenylacetic acid metabolism in bacteria. The elucidation of the structure of the PaaX repressor allows a better understanding of the regulation of phenylacetic acid metabolism in bacteria.](/sites/default/files/2023-12/imagen_web.jpg)
The PaaX protein is the major regulator of the phenylacetic acid pathway in Escherichia coli, a central pathway for bacterial aerobic degradation of aromatic compounds. In a new study result of an international collaboration, researchers from Spanish, English, and Australian institutions elucidated the three-dimensional structure of this protein and its stability. Dr. Jesús Miguel Sanz Morales, from the Margarita Salas Center for Biological Research (CIB-CSIC), and Dr. Juan Hermoso, from the Blas Cabrera Institute of Physical Chemistry (IQF-CSIC), led the research, which has been published in the International Journal of Biological Macromolecules.
Aromatic compounds come from different sources and are abundant in soil and water. They are highly resistant to biodegradation, and their biological transformation is usually carried out by bacteria and fungi. In particular, the degradation of phenylacetic acid (PAA) and its derivatives can be carried out by several bacteria and fungi both in aerobic and anaerobic conditions.
The PAA degradation routes constitute the main metabolic pathway for aromatic compounds in bacteria, being present in around 16 % of the bacterial sequence genome. However, despite its widespread presence in the microbial realm, the role of PAA is still largely unknown. Furthermore, in some cases, the PAA pathway has been related to the accumulation of toxic metabolic intermediates that promote the virulence of multiple pathogens. Therefore, the study of the PAA pathway and its regulation could contribute to improving the application of microorganisms in environmental and biotechnological processes, as well as clarifying health problems such as bacterial pathogenicity and resistance to antimicrobials.
PaaX is a transcriptional repressor of the PAA aerobic degradation pathway. Under normal conditions, PaaX is associated with three promoter sequences (Pa, Px, and Pz), and through this binding it represses the expression of the enzymes of the pathway. The first step in the aerobic degradation of PAA is its esterification with coenzyme A (CoA), leading to the formation of phenylacetyl-coenzyme A (PA-CoA). When this compound is bound to PaaX, the regulator dissociates from the genetic sequences to which it is associated, causing activation of the pathway. Although this function is known, the mechanisms by which PaaX binds to DNA and its inducer PA-CoA and thereby represses or enables transcription are not yet understood. Now, this work published in International Journal of Biological Macromolecules has elucidated the crystallographic structure of PaaX, providing important clues to understanding these mechanisms.
The structural analysis performed in the study shows that PaaX possesses a new type of folding, which has not been observed so far in transcriptional repressors in prokaryotes. As suggested by the authors, these results provide valuable information to better understand the stability and mechanism of PaaX and pave the way for further analysis of other regulators with similar structural configurations.
Reference: Structural characterization of PaaX, the main repressor of the phenylacetate degradation pathway in Escherichia coli W: A novel fold of transcription regulator proteins. V. M. Hernández-Rocamora, R. Molina, A. Alba, C. Carrasco-López, A. Rojas-Altuve, S. Panjikar, A. Medina, I. Usón, C. Alfonso, B. Galán, G. Rivas, J. A. Hermoso, J. M. Sanz. https://doi.org/10.1016/j.ijbiomac.2023.127935