A Density Functional Theory Study of the Iron-Binding Site of Human Serum Transferrin
Human serum transferrin binds ferric ions with high affinity in the blood stream and releases them into cells by a process involving receptor-mediated endocytosis and a decrease in pH. The iron-release mechanism is unclear but protonation events and conformational changes are known to be important. In this study, we investigate properties of the iron-binding site theoretically. Our results suggest that an equatorial histidine could be in its histidinate form when bound to iron at neutral and high pH and that protonation of an axial tyrosine is a key event in iron release. Support for this mechanism from other metal-binding enzymes is also presented.
Background ::: T2 hyperintensities (T2H) on MRI are the most common CNS lesions in individuals with neurofibromatosis type 1 (NF1).