8HJB

Crystal structure of Pseudomonas aeruginosa PvrA with coenzyme A

Summary for 8HJB

• Entry DOI: 10.2210/pdb8hjb/pdb
• Related: 7Y0Y 7Y0Z
• Descriptor: TetR family transcriptional regulator, COENZYME A (3 entities in total)
• Functional Keywords: tetr family, transcription factor, transcription
• Biological source: Pseudomonas aeruginosa PA14
• Total number of polymer chains: 2
• Total formula weight: 50911.07

Authors

Liang, H.,Bartlam, M. (deposition date: 2022-11-23, release date: 2023-02-08, Last modification date: 2024-05-29)

Primary citation

Pan, X.,Liang, H.,Zhao, X.,Zhang, Q.,Chen, L.,Yue, Z.,Yin, L.,Jin, Y.,Bai, F.,Cheng, Z.,Bartlam, M.,Wu, W.
Regulatory and structural mechanisms of PvrA-mediated regulation of the PQS quorum-sensing system and PHA biosynthesis in Pseudomonas aeruginosa.
Nucleic Acids Res., 51:2691-2708, 2023

PubMed Abstract: Pseudomonas aeruginosa is capable of causing acute and chronic infections in various host tissues, which depends on its abilities to effectively utilize host-derived nutrients and produce protein virulence factors and toxic compounds. However, the regulatory mechanisms that direct metabolic intermediates towards production of toxic compounds are poorly understood. We previously identified a regulatory protein PvrA that controls genes involved in fatty acid catabolism by binding to palmitoyl-coenzyme A (CoA). In this study, transcriptomic analyses revealed that PvrA activates the Pseudomonas quinolone signal (PQS) synthesis genes, while suppressing genes for production of polyhydroxyalkanoates (PHAs). When palmitic acid was the sole carbon source, mutation of pvrA reduced production of pyocyanin and rhamnolipids due to defective PQS synthesis, but increased PHA production. We further solved the co-crystal structure of PvrA with palmitoyl-CoA and identified palmitoyl-CoA-binding residues. By using pvrA mutants, we verified the roles of the key palmitoyl-CoA-binding residues in gene regulation in response to palmitic acid. Since the PQS signal molecules, rhamnolipids and PHA synthesis pathways are interconnected by common metabolic intermediates, our results revealed a regulatory mechanism that directs carbon flux from carbon/energy storage to virulence factor production, which might be crucial for the pathogenesis.

PubMed: 36744476
DOI: 10.1093/nar/gkad059

Experimental method

X-RAY DIFFRACTION (2.65 Å)