Probing redox potential for Iron sulfur clusters in photosystem I

TL;DR

This study uses computational methods to explain why the FX iron sulfur cluster in Photosystem I has a lower oxidation potential than FA and FB, revealing the electrostatic interactions responsible for this difference.

Contribution

The paper provides a detailed computational analysis of the electrostatic factors influencing redox potentials of iron sulfur clusters in Photosystem I, clarifying the molecular basis of their differences.

Findings

FX has the lowest oxidation potential due to strong electrostatic interactions.

Shorter Fe-S bond distances in FX contribute to its lower potential.

Results align with experimental redox titration data.

Abstract

Photosystem I is a light-driven electron transfer device. Available X-ray crystal structure from Thermosynechococcus elongatus, showed that electron transfer pathways consist of two nearly symmetric branches of cofactors converging at the first iron sulfur cluster FX, which is followed by two terminal iron sulfur clusters FA and FB. Experiments have shown that Fx has lower oxidation potential than FA and FB, which facilitate the electron transfer reaction. Here, we use Density Functional Theory and Multi-Conformer Continuum Electrostatics to explain the differences in the midpoint Em potentials of the Fx, FA and FB clusters. Our calculations show that Fx has the lowest oxidation potential compared to FA and FB due strong pair-wise electrostatic interactions with surrounding residues. These interactions are shown to dominated by the bridging sulfurs and cysteine ligands, which may be attributed to the shorter average bond distances between the oxidized Fe ion and ligating sulfurs for FX compared to FA and FB. Moreover, the electrostatic repulsion between the 4Fe-4S clusters and the positive potential of the backbone atoms is least for FX compared to both of FA and FB. These results agree with the experimental measurements from the redox titrations of low-temperature EPR signals and of room temperature recombination kinetics.