Tetraphenylporphyrin Enters the Ring: First Example of a Complex between Highly Bulky Porphyrins and a Protein

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. Joining the race: The native haemoprotein HasA can be coaxed into capturing extremely bulky and water‐insoluble metallotetraphenylporphyrins (metalloTPPs). The reproducible, rapid crystallisation of metalloTPP‐HasA was possible at excellent resolutions, revealing in rich detail of how different metalloTPPs are accommodated by HasA. Furthermore, the combination of TPP chemistry with HasA enables the inactivation of multiple strains of multidrug‐resistant Pseudomonas aeruginosa as well as the cyclopropanation of styrene.