9KOI

Crystal structure of ExaC, an NAD+-dependent aldehyde dehydrogenase, from Pseudomonas aeruginosa

Summary for 9KOI

• Entry DOI: 10.2210/pdb9koi/pdb
• Descriptor: NAD+ dependent aldehyde dehydrogenase ExaC (2 entities in total)
• Functional Keywords: exac; crystal structure; nad+-dependent aldehyde dehydrogenase;, oxidoreductase
• Biological source: Pseudomonas aeruginosa PAO1
• Total number of polymer chains: 2
• Total formula weight: 110066.98

Authors

Lee, J.Y.,Ko, J.H.,Jeong, K.H.,Son, S.B. (deposition date: 2024-11-20, release date: 2024-12-11, Last modification date: 2025-01-29)

Primary citation

Ko, J.H.,Jeong, K.H.,Son, S.B.,Lee, J.Y.
Structural analysis of ExaC, an NAD + -dependent aldehyde dehydrogenase, from Pseudomonas aeruginosa.
Biochem.Biophys.Res.Commun., 742:151077-151077, 2025

PubMed Abstract: The opportunistic pathogen Pseudomonas aeruginosa (Pa) utilizes ethanol as an energy source, however, ethanol metabolism generates acetaldehyde, a toxic byproduct. To mitigate this toxicity, P. aeruginosa employs aldehyde dehydrogenases (ALDHs) to oxidize acetaldehyde into less harmful compounds. ExaC, an NAD-dependent ALDH from P. aeruginosa (PaExaC) and a member of group X ALDHs, plays a critical role in this detoxification by oxidizing both aldehydes and hydrazones. In this study, we determined the crystal structures of PaExaC in its apo and NAD -bound forms. PaExaC functions as a homodimer, with three distinct domains: an NAD binding domain, a catalytic domain, and an oligomerization domain. Structural analyses revealed that PaExaC's substrate entry channel (SEC) is optimized for size-selective aldehyde metabolism, with Leu120, Tyr462, and Thr302. Comparative structural and docking analyses with other ALDHs further validated PaExaC's preference for small aliphatic aldehydes and hydrazones. These findings highlight PaExaC's role in aldehyde detoxification, facilitating P. aeruginosa survival in diverse environments, and provide structural insights for developing targeted inhibitors to help treat infections.

PubMed: 39642707
DOI: 10.1016/j.bbrc.2024.151077

Experimental method

X-RAY DIFFRACTION (2.4 Å)