6B4R

The crystal structure of the aldehyde dehydrogenase KauB from Pseudomonas aeruginosa

Summary for 6B4R

• Entry DOI: 10.2210/pdb6b4r/pdb
• Descriptor: KauB, 1,2-ETHANEDIOL, POTASSIUM ION, ... (7 entities in total)
• Functional Keywords: aldehyde dehydrogenase, kaub, oxidoreductase
• Biological source: Pseudomonas aeruginosa PAO1; More
• Total number of polymer chains: 4
• Total formula weight: 213859.25

Authors

Gonzalez-Segura, L.,Cardona-Cardona, Y.,Carrillo-Campos, J.,Munoz-Clares, R.A. (deposition date: 2017-09-27, release date: 2018-10-03, Last modification date: 2025-04-30)

Primary citation

Cardona-Cardona, Y.V.,Gonzalez-Segura, L.,Rodriguez-Sotres, R.,Juarez-Diaz, J.A.,Mujica-Jimenez, C.,Regla, I.,Lopez-Ortiz, M.,Munoz-Clares, R.A.
The structural basis for the broad aldehyde specificity of the aminoaldehyde dehydrogenase PauC from the human pathogen Pseudomonas aeruginosa.
Protein Sci., 34:e70124-e70124, 2025

PubMed Abstract: Despite significant differences in size and formal charge, the aldehyde dehydrogenase PaPauC (PA5312) from Pseudomonas aeruginosa PAO1 efficiently catalyzes the NAD-dependent oxidation of the aminoaldehydes formed in polyamines degradation. We report here that PaPauC also oxidizes 4-guanidinebutyraldehyde, formed in one arginine degradation pathway, trimethylaminobutyraldehyde, of unknown metabolic origin, and indole-3-acetaldehyde, a precursor of the plant growth-promoting hormone indoleacetic acid. PaPauC has been proposed as a potential target for combating P. aeruginosa. However, understanding its structure-function relationships, crucial for developing specific inhibitors, is lacking. Using X-ray crystallography, we identified the structural characteristics that determine PaPauC broad aldehyde specificity: a spacious aldehyde-entrance tunnel and six active-site residues. Docking simulations, site-directed mutagenesis, and kinetic analyses support the interactions of Lys479 with glutamylated aminoaldehydes; Phe169, Trp176, and Phe467 with amino and guanidinium groups through cation-π interactions and with the indole group via NH-π and CH-π interactions; Asp459 with amino and indole groups; and Thr303 with amide and guanidinium groups. Exploiting the distinctive structural features of the PaPauC active site could aid in developing specific inhibitors to combat P. aeruginosa infections in humans and animals, as well as in preventing its colonization of plants, which are abundant P. aeruginosa reservoirs and, therefore, a significant source of human infections.

PubMed: 40248884
DOI: 10.1002/pro.70124

Experimental method

X-RAY DIFFRACTION (2.55 Å)