The Reversible Opening of Water Channels in Cytochrome c Modulates the Heme Iron Reduction Potential

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• 作者：Carlo Augusto Bortolotti ; Andrea Amadei ; Massimiliano Aschi ; Marco Borsari ; Stefano Corni ; Marco Sola ; Isabella Daidone
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：August 22, 2012
• 年：2012
• 卷：134
• 期：33
• 页码：13670-13678
• 全文大小：491K
• 年卷期：v.134,no.33(August 22, 2012)
• ISSN：1520-5126

文摘

Dynamic protein鈥搒olvent interactions are fundamental for life processes, but their investigation is still experimentally very demanding. Molecular dynamics simulations up to hundreds of nanoseconds can bring to light unexpected events even for extensively studied biomolecules. This paper reports a combined computational/experimental approach that reveals the reversible opening of two distinct fluctuating cavities in Saccharomyces cerevisiae iso-1-cytochrome c. Both channels allow water access to the heme center. By means of a mixed quantum mechanics/molecular dynamics (QM/MD) theoretical approach, the perturbed matrix method (PMM), that allows to reach long simulation times, changes in the reduction potential of the heme Fe³⁺/Fe²⁺ couple induced by the opening of each cavity are calculated. Shifts of the reduction potential upon changes in the hydration of the heme propionates are observed. These variations are relatively small but significant and could therefore represent a tool developed by cytochrome c for the solvent driven, fine-tuning of its redox functionality.