Solution structures of chloroquine-ferriheme complexes modeled using MD simulation and investigated by EXAFS spectroscopy.

Solution structures of chloroquine-ferriheme complexes modeled using MD simulation and investigated by EXAFS spectroscopy. J Inorg Biochem. 2015 Jun 11; Authors: Kuter D, Streltsov V, Davydova N, Venter GA, Naidoo KJ, Egan TJ Abstract The interaction of chloroquine (CQ) and the μ-oxo dimer of iron(III) protoporphyrin IX (ferriheme) in aqueous solution was modeled using molecular dynamics (MD) simulations. Two models of the CQ-(μ-oxo ferriheme) complex were investigated, one involving CQ π-stacked with an unligated porphyrin face of μ-oxo ferriheme and the other in which CQ was docked between the two porphyrin rings. The feasibility of both models was tested by fitting computed structures to the experimental extended X-ray absorption fine structure (EXAFS) spectrum of the CQ-(μ-oxo ferriheme) complex in frozen aqueous solution. The docked model produced better agreement with experimental data, suggesting that this is the more likely structure in aqueous solution. The EXAFS fit indicated a longer than expected Fe-O bond of 1.87Å, accounting for the higher than expected magnetic moment of the complex. As a consequence, the asymmetric Fe-O-Fe stretch shifts much lower in frequency and was identified in the precipitated solid at 744cm(-1) with the aid of the O(18) isomer shift. Three important CQ-ferriheme interactions were identified in the docked structure. These were a hydrogen bond between the oxide bridge of μ-oxo ferriheme an...
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research
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