Ferritins are ubiquitous and conserved proteins endowed with enzymatic ferroxidase activity, that oxidize Fe(II) ions at the dimetal ferroxidase centre to form a mineralized Fe(III) oxide core deposited within the apo-protein shell. Herein, the in vitro formation of a heterodimetal cofactor constituted by Fe and Mn ions has been investigated in human H ferritin (hHFt). Namely, Mn and Fe binding at the hHFt ferroxidase centre and its effects on Fe(II) oxidation have been investigated by UV–Vis ferroxidation kinetics, fluorimetric titrations, multifrequency EPR, and preliminary Mössbauer spectroscopy. Our results show that in hHFt, both Fe(II) and Mn(II) bind the ferroxidase centre forming a Fe-Mn cofactor. Moreover, molecular oxygen seems to favour Mn(II) binding and increases the ferroxidation activity of the Mn-loaded protein. The data suggest that Mn influences the Fe binding and the efficiency of the ferroxidation reaction. The higher efficiency of the Mn-Fe heterometallic centre may have a physiological relevance in specific cell types (i.e. glia cells), where the concentration of Mn is the same order of magnitude as iron.

铁蛋白是普遍存在且具有保守性的蛋白，具有酶促铁氧化酶活性，可在双金属铁氧化酶中心氧化Fe（II）离子，形成沉积在脱辅基蛋白壳中的矿化Fe（III）氧化核。在本文中，已经在人H铁蛋白（hHFt）中研究了由Fe和Mn离子构成的异双金属辅因子的体外形成。即，已通过UV-Vis铁氧化动力学，荧光滴定，多频EPR和初步Mössbauer光谱研究了hHFt铁氧化酶中心的Mn和Fe结合及其对Fe（II）氧化的影响。我们的研究结果表明，在hHFt中，Fe（II）和Mn（II）都与铁氧化酶中心结合，形成Fe-Mn辅因子。此外，分子氧似乎有利于Mn（II）结合并增加了Mn负载蛋白的铁氧化活性。数据表明Mn影响Fe结合和铁氧化反应的效率。Mn-Fe杂金属中心的更高效率可能与特定细胞类型具有生理相关性（即神经胶质细胞），其中Mn的浓度与铁相同。