Selective binding of antimicrobial porphyrins to the heme‐receptor IsdH‐NEAT3 of Staphylococcus aureus

摘要: The Isd (iron-regulated surface determinant) system of the human pathogen Staphylococcus aureus is responsible for acquisition heme from host organism. We recently reported that extracellular receptor IsdH-NEAT3 captures and transfers noniron antimicrobial porphyrins containing metals in oxidation state (III). However, it unclear if geometric factors such as size metal (ionic radius) affect binding transfer metalloporphyrins. carried out an ample structural, functional, thermodynamic analysis properties indium(III)-porphyrin, which bears a much larger ion than iron(III) natural ligand heme. results demonstrate NEAT3 recognizes In(III)-containing PPIX manner very similar to Site-directed mutagenesis identifies Tyr642 central element recognition mechanism suggested crystal structures. Importantly, possesses remarkable ability capture dimers metalloporphyrin. Molecular dynamics simulations reveal does not require conformational changes, or large rearrangements residues within its site, accommodate (heme)2 ligand. discuss implications these findings design potent inhibitors against this family key receptors S. aureus.