Rapid Heme Transfer Reactions between NEAr Transporter Domains of Staphylococcus aureus: A Theoretical Study Using QM/MM and MD Simulations

摘要: In vertebrates, most iron is present as heme or chelated by proteins. Thus, Gram-positive pathogens such Staphylococcus aureus have evolved an iron-regulated surface determinant (Isd) system that transports across thick cell walls into the cytoplasm. Recent studies demonstrated rapidly transferred between NEAr Transporter (NEAT) domains of Isd system, despite its high affinity toward each domain, suggesting presence intermediate NEAT•heme•NEAT complex. study, we performed short restrained molecular dynamics (MD) simulations to dock acceptor NEAT domain donor NEAT•heme complex and obtained models where two were arranged with two-fold pseudo symmetry around molecule. After turning off restraints, structures stably maintained during subsequent unrestrained MD simulations, except for hydrogen bond propionate group molecule potentially facilitating transition from acceptor. Subsequent structural optimization using quantum mechanics/molecular mechanics (QM/MM) method showed tyrosine residues, one simultaneously coordinated ferric in only if they deprotonated. Based on these results, propose a reaction scheme transfer domains.