Heme-substituted protein assembly bridged by synthetic porphyrin: achieving controlled configuration while maintaining rotational freedom.

The use of biological host-guest interactions, specifically the binding of hemoprotein to heme, has attracted significant research interest in the design of artificial protein assemblies. However, because of the inherent flexibility of the propionic acid group of heme, it is difficult to control the positioning and orientation of the protein unit and to construct well-ordered structures. Herein, we report a heme-substituted protein dimer composed of the native hemoprotein HasA, which accommodates a tetraphenylporphyrin bearing an additional metal coordination site.

A Compound I Mimic Reveals the Transient Active Species of a Cytochrome P450 Enzyme: Insight into the Stereoselectivity of P450-Catalysed Oxidations.

Catching the structure of cytochrome P450 enzymes in flagrante is crucial for the development of P450 biocatalysts, as most structures collected are found trapped in a precatalytic conformation. At the heart of P450 catalysis lies Cpd I, a short-lived, highly reactive intermediate, whose recalcitrant nature has thwarted most attempts at capturing catalytically relevant poses of P450s. We report the crystal structure of P450BM3 mimicking the state in the precise moment preceding epoxidation, which is in perfect agreement with the experimentally observed stereoselectivity.

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.

Enhanced - and enantioselective cyclopropanation of styrene catalysed by cytochrome P450BM3 using decoy molecules.

We report the enhanced cis- and enantioselective cyclopropanation of styrene catalysed by cytochrome P450BM3 in the presence of dummy substrates, i.e. decoy molecules.

Hijacking the Heme Acquisition System of for the Delivery of Phthalocyanine as an Antimicrobial.

To survive in the iron-devoid environment of their host, pathogenic bacteria have devised multifarious cunning tactics such as evolving intricate heme transport systems to pirate extracellular heme. Yet, the potential of heme transport systems as antimicrobial targets has not been explored. Herein we developed a strategy to deliver antimicrobials by exploiting the extracellular heme acquisition system protein A (HasA) of .

Highly malleable haem-binding site of the haemoprotein HasA permits stable accommodation of bulky tetraphenylporphycenes.

Iron(iii)- and cobalt(iii)-9,10,19,20-tetraphenylporphycenes, which possess bulky phenyl groups at the four positions of porphycene, were successfully incorporated into the haem acquisition protein HasA secreted by . Crystal structure analysis revealed that loops surrounding the haem-binding site are highly flexible, remodelling themselves to accommodate bulky metal complexes with significantly different structures from the native haem cofactor.

Structures of the Heme Acquisition Protein HasA with Iron(III)-5,15-Diphenylporphyrin and Derivatives Thereof as an Artificial Prosthetic Group.

Iron(III)-5,15-diphenylporphyrin and several derivatives were accommodated by HasA, a heme acquisition protein secreted by Pseudomonas aeruginosa, despite possessing bulky substituents at the meso position of the porphyrin. Crystal structure analysis revealed that the two phenyl groups at the meso positions of porphyrin extend outside HasA. It was shown that the growth of P.