Tetraphenylporphyrin (TPP) is a symmetrically substituted synthetic porphyrin whose properties can be readily modified, providing it with significant advantages over naturally occurring porphyrins. Herein, we report the first example of a stable complex between a native biomolecule, the haemoprotein HasA, and TPP as well as its derivatives. The X‐ray crystal structures of nine different HasA‐TPP complexes were solved at high resolutions. HasA capturing TPP derivatives was also demonstrated to inhibit growth of the opportunistic pathogen Pseudomonas aeruginosa. Mutant variants of HasA binding FeTPP were shown to possess a different mode of coordination, permitting the cyclopropanation of styrene.
Using artificial hemes for the reconstruction of natural heme proteins represents a fascinating approach to enhance the bioactivity of the latter. We report the synthesis of various metal 5-oxaporphyrinium cations as cofactors, and a cobalt 5-oxaporphyrinium cation was successfully incorporated into the heme-acquisition protein (HasA) secreted by Pseudomonas aeruginosa. We hypothesize that the oxaporphyrinium cation strongly binds to the HasA-specific outer membrane receptor (HasR) due to its cationic charge, which prevents the subsequent acquisition of heme. In fact, the reconstructed HasA inhibited the growth of Pseudomonas aeruginosa and even of multidrug-resistant P. aeruginosa.
Tetraphenylporphyrin (TPP) is a synthetic porphyrin whose properties can be readily modified, endowing it with significant benefits over naturally occurring porphyrins. Yet, their insolubility in water and/or steric bulk have rendered them incompatible with biological systems. Herein, we report the first example of a native biomolecule capturing TPP as well as its derivatives. The haemoprotein HasA, secreted by certain pathogens to scavenge haem from their hosts, can capture various metal- and meso-substituted TPPs. The rapid crystallisation of TPP derivatives captured by HasA revealed the binding mode of TPP at excellent resolutions. A single-site mutation (L85A) of HasA enlarged the binding pocket, allowing the incorporation of a bulkier derivative of TPP. HasA binding TPP derivatives was also demonstrated to inhibit proliferation of the opportunistic pathogen Pseudomonas aeruginosa. This study not only represents a simple method for the complexation of TPP derivatives with a native protein, but also opens the door for the future use of TPP derivatives as biological tools.
Using artificial hemes for the reconstruction of natural heme proteins represents a fascinating approach to enhance the bioactivity of the latter. We report the synthesis of various metal 5-oxaporphyrinium cations as cofactors, and a cobalt 5-oxaporphyrinium cation was successfully incorporated into the heme-acquisition protein (HasA) secreted by Pseudomonas aeruginosa. We hypothesize that the oxaporphyrinium cation strongly binds to the HasA-specific outer membrane receptor (HasR) due to its cationic charge, which prevents the subsequent acquisition of heme. In fact, the reconstructed HasA inhibited the growth of Pseudomonas aeruginosa and even of multidrug-resistant P. aeruginosa.
Metallotetraphenylporphyrins (metalloTPPs) are exceedingly hydrophobic, rendering them insoluble in aqueous solvents. Upon introduction of the bacterial haem‐acquisition protein, HasA, which can incorporate bulky metalloTPPs in its haem‐binding pocket, a stable, water‐soluble HasA–TPP complex can be formed. This permits the utilisation of metalloTPPs, in the form of a HasA–TPP complex, with biological systems, as antimicrobial agents targeting the critical pathogen Pseudomonas aeruginosa or as biocatalysts. The picture was created by Yuma Shisaka and Mami Yoshimura. More information can be found in the Research Article by O. Shoji et al.
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