Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Proteins. 2013 Jun;81(6):1042-50. doi: 10.1002/prot.24251. Epub 2013 Apr 1.
We study via all atom classical molecular dynamics (MD) simulation the process of uptake of ferrous ions (Fe(2+)) into the human ferritin protein and the catalytic ferroxidase sites via pores ("channels") in the interior of the protein. We observe that the three-fold hydrophilic channels serve as the main entrance pathway for the Fe(2+) ions. The binding sites along the ion pathway are investigated. Two strong binding sites, at the Asp131 and Glu134 residues and two weak binding sites, at the His118 and Cys130 are observed inside the three-fold channel. We also identify an explicit pathway for an ion exiting the channel into the central core of the protein as it moves to the ferroxidase site. The diffusion of an Fe(2+) ion from the inner opening of the channel to a ferroxidase site located in the interior region of the protein coat is assisted by Thr135, His136 and Tyr137. The Fe(2+) ion binds preferentially to site A of the ferroxidase site.
我们通过全原子经典分子动力学 (MD) 模拟研究了亚铁离子 (Fe(2+)) 通过蛋白质内部的孔隙（“通道”）进入人铁蛋白和催化铁氧化酶部位的过程。我们观察到三折叠亲水通道是 Fe(2+) 离子的主要入口途径。研究了离子通道沿线的结合位点。在三折叠通道内观察到两个强结合位点，位于 Asp131 和 Glu134 残基处，以及两个弱结合位点，位于 His118 和 Cys130 残基处。我们还确定了离子从通道进入蛋白质中心核的明确途径，因为它移动到铁氧化酶部位。Fe(2+) 离子从通道的内开口扩散到位于蛋白质外壳内部区域的铁氧化酶部位，由 Thr135、His136 和 Tyr137 协助。Fe(2+) 离子优先结合到铁氧化酶部位的 A 位。
