8WCO

(S)-citramalyl-CoA lyase

Summary for 8WCO

• Entry DOI: 10.2210/pdb8wco/pdb
• Descriptor: Probable acyl-CoA lyase beta chain, ACETYL COENZYME *A (3 entities in total)
• Functional Keywords: (s)-citramalyl-coa lyase, lyase
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 3
• Total formula weight: 89603.70

Authors

Huang, Q.,Bao, R. (deposition date: 2023-09-13, release date: 2024-05-15, Last modification date: 2024-07-24)

Primary citation

Huang, Q.,Duan, C.,Ma, H.,Nong, C.,Zheng, Q.,Zhou, J.,Zhao, N.,Mou, X.,Liu, T.,Zou, S.,Yang, N.,Tong, A.,Qin, W.,Bao, R.
Structural and functional characterization of itaconyl-CoA hydratase and citramalyl-CoA lyase involved in itaconate metabolism of Pseudomonas aeruginosa.
Structure, 32:941-952.e3, 2024

PubMed Abstract: Itaconate is a key anti-inflammatory/antibacterial metabolite in pathogen-macrophage interactions that induces adaptive changes in Pseudomonas aeruginosa-exposed airways. However, the impact and mechanisms underlying itaconate metabolism remain unclear. Our study reveals that itaconate significantly upregulates the expression of pyoverdine in P. aeruginosa and enhances its tolerance to tobramycin. Notably, the enzymes responsible for efficient itaconate metabolism, PaIch and PaCcl, play crucial roles in both utilizing itaconate and clearing its toxic metabolic intermediates. By using protein crystallography and molecular dynamics simulations analyses, we have elucidated the unique catalytic center and substrate-binding pocket of PaIch, which contribute to its highly efficient catalysis. Meanwhile, analysis of PaCcl has revealed how interactions between domains regulate the conformational changes of the active sites and binding pockets, influencing the catalytic process. Overall, our research uncovers the significance and mechanisms of PaIch and PaCcl in the efficient metabolism of itaconate by P. aeruginosa.

PubMed: 38677288
DOI: 10.1016/j.str.2024.04.004

Experimental method

X-RAY DIFFRACTION (2.6 Å)