Resumo

MUNOZ-CLARES, Rosario A.; FERNANDEZ-SILVA, Arline; MUJICA-JIMENEZ, Carlos  e  MARTINEZ-FLORES, Sebastian. Substrate Specificity in Promiscuous Enzymes: The Case of the Aminoaldehyde Dehydrogenases from Pseudomonas aeruginosa. J. Mex. Chem. Soc [online]. 2023, vol.67, n.3, pp.240-250.  Epub 22-Abr-2024. ISSN 1870-249X.  https://doi.org/10.29356/jmcs.v67i3.2022.

Substrate specificity is instrumental in enzyme catalysis and a major determinant of the enzyme’s physiological role. Nevertheless, the degree of substrate specificity may vary in an ample range; some enzymes exhibit very high specificity while others show a relaxed specificity or promiscuity. The latter is used by evolution for the emergence of new enzymes able to perform novel metabolic roles. The basis of substrate specificity is substrate recognition, which is achieved in the enzyme active site by chemical and structural mechanisms. Here, we exemplify that specificity may exist within promiscuity by comparatively analyzing kinetic and structural data of the four Pseudomonas aeruginosa aminoaldehyde dehydrogenases-PA5373, PA5312, PA4189, and PA0219. Despite their apparent substrate promiscuity, we found that these enzymes show a significant degree of substrate specificity. They have evolved to preferentially oxidize different aminoaldehydes, even though each of them can use as in vitro substrates most of the aminoaldehydes preferred by the others. We focus on the role played in these enzymes by two active-site residues-one acidic and the other aromatic, both belonging to the so-called “anchor” loop-in binding the aldehyde amino group, as well as on the importance of the anchor loop conformation in defining the size and shape of the active-site cavity. Our results support the notion that natural selection has fine-tuned the active-site structural and chemical features of the P. aeruginosa AMADH enzymes to the structural and chemical features of their physiological aminoaldehydes substrates.

Palavras-chave : Aldehyde dehydrogenase; physiological substrate; structure-function relationships; active-site residues; active-site conformation.

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