Effects of Hinge-Loop Mutation on Electron Transfer Rate between Two Heme Groups in Cytochrome c Heterodimer
Kohei Ishikawa1 , Hirotaka Kitoh-Nishioka2,3, Ryuhei Harada3, Mitsuo Shoji3, and Yasuteru Shigeta3
1 Graduate School of Pure and Applied Sciences, University of Tsukuba, Japan
2 JST-PRESTO, Japan
3 Center for Computational Sciences, University of Tsukuba, Japan
Cytochrome-c (Cyt c) is a soluble hemeprotein and plays an essential role for electron transport in the respiratory chain. If the Cyt c is polymerized after denaturation, the electron transport function is lost and severe diseases are caused. Hirota et al. solved X-ray structures of oxidized Cyt c dimer and trimer derived from a horse, and they determined that the denatured Cyt c monomers continuously forms their polymer structure with domain swaps of the N-terminal domain [1]. By using a theoretical approach, the homodimer of Cyt c was shown to be extremely stable [2]. Zhang et al. have synthesized an artificial Cyt c that consists of two different Cyt c (Pseudomonas aeruginosa (PA) Cyt c551 and Hydrogenobacter thermophilus (HT) Cyt c552) with a mutual exchange of N-terminal domain. For such heterodimer, a little redox difference exists between two heme irons, and electron transfer dynamics can be observed after reduction.
In the present study, molecular dynamics (MD) simulations of the heterodimer were performed for the representative structures of the artificial Cyt c in the aqueous solution. For these structures, we have analyzed the electron transfer coupling constants by using a pathways plugin implemented in the VMD program [4,5]. In order to investigate the mutational effects on hinge-loop, we modeled some mutants by introducing amino acids with aromatic groups and the electron transfer coupling constants were compared with the original ones. We have also evaluated the electron coupling constants from extended Hückel calculations [6]. Results are presented in this poster.
References
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