8J4H

X-ray structure of a ferric ion-binding protein A (FbpA) from Vibrio metschnikovii in complex with Danshensu (DSS)

Summary for 8J4H

• Entry DOI: 10.2210/pdb8j4h/pdb
• Descriptor: Ferric iron ABC transporter iron-binding protein, (2~{R})-3-[3,4-bis(oxidanyl)phenyl]-2-oxidanyl-propanoic acid (3 entities in total)
• Functional Keywords: ferric binding protein, fbpa, danshensu, vibrio metschnikovii, metal binding protein
• Biological source: Vibrio metschnikovii
• Total number of polymer chains: 1
• Total formula weight: 33698.93

Authors

Lu, P.,Jiang, J.,Nagata, K. (deposition date: 2023-04-20, release date: 2024-01-10, Last modification date: 2024-02-07)

Primary citation

Lu, P.,Jiang, J.,Liu, C.,Okuda, S.,Itoh, H.,Okamoto, K.,Suzuki, M.,Nagata, K.
Molecular mechanism of Fe 3+ binding inhibition to Vibrio metschnikovii ferric ion-binding protein, FbpA, by rosmarinic acid and its hydrolysate, danshensu.
Protein Sci., 33:e4881-e4881, 2024

PubMed Abstract: Global warming has increased the growth of pathogenic Vibrio bacteria, which can cause foodborne illnesses and death. Vibrio bacteria require iron for growth and survival. They utilize a ferric ion-binding protein (FbpA) to bind and transport Fe into the cell. FbpA from Vibrio metschnikovii (Vm) is a potential target for inhibiting its growth. Rosmarinic acid (RA) can block the binding of VmFbpA to Fe ; however, the molecular mechanism of Fe binding and RA inhibition to VmFbpA is unclear. In this study, we used x-ray crystallography to determine the Fe -binding mode of VmFbpA and the mechanism of RA inhibition. The structures revealed that in the Fe bound form, Fe was coordinated to VmFbpA by two Tyr residues, two HCO ions, and two water molecules in a six-coordinated geometry. In contrast, in the inhibitor bound form, RA was initially bound to VmFbpA following gel filtration purification, but it was hydrolyzed to danshensu (DSS), which occupied the binding site as shown in an electron density map and reverse phase chromatography (RPC) analysis. Both RA and DSS exhibited a stronger binding affinity to VmFbpA, higher Fe reduction capacity, and more potent bacteriostatic effect on V. metschnikovii compared with caffeic acid (CA), another hydrolysis product of RA. These results provide insight into the mechanism of iron acquisition by V. metschnikovii and inhibition by RA and DSS. Our findings offer clues on the development of effective strategies to prevent Vibrio infections.

PubMed: 38143427
DOI: 10.1002/pro.4881

Experimental method

X-RAY DIFFRACTION (2.01 Å)