# Electronic and Structural Heterogeneity in the Diiron Center of Sulerythrin: Insights From Hybrid QM/MM Calculations

## TL;DR

This paper uses computer modeling to understand the structure and function of a diiron center in a protein from a type of bacteria.

## Contribution

The study identifies three distinct electronic states of the diiron center in Sulerythrin using QM/MM calculations.

## Key findings

- Three electronic states of the diFe-SulE center were identified, involving different ligands and protonation states.
- The findings align with structural heterogeneity observed in crystallography and explain the enzyme's reactivity.
- QM/MM modeling provides subatomic insights into nonheme diiron enzyme function.

## Abstract

Sulerythrins (SulE) are ferritin‐like proteins from obligate aerobes such as Sulfolobus tokodaii, forming a domain‐swapped dimer with a four‐helix‐bundle scaffold and a heterobimetallic Fe–Zn center. The diFe‐SulE variant resembles diiron carboxylate proteins and contains two bimetallic active sites coordinated by histidines, glutamates, and bridging oxo ligands. High‐resolution crystallography revealed slight differences in Fe–Fe distances and mixed‐valence states, but the precise chemical nature of the oxo species remains unclear. To clarify the electronic and structural properties of diFe‐SulE, we performed hybrid quantum mechanical/molecular mechanics (QM/MM) calculations on models varying in protonation, dioxo ligands, and iron redox states of the active site. Our results reveal at least three electronic states for diFe‐SulE: (i) a diferrous center with an end‐on di‐μ‐hydroperoxo ligand; (ii) a diferric center with hydroxo ligands interacting with protonated Glu95; and (iii) a diferrous center bridged by a di‐μ‐peroxo ligand, also interacting with protonated Glu95. These states are consistent with the structural heterogeneity observed experimentally. Overall, the hybrid QM/MM approach refines the crystallographic models and offers subatomic‐level insight into the electronic structure and reactivity of the SulE diiron center, deepening our understanding of nonheme diiron enzymes.

QM/MM modeling of Sulerythrin (SulE) identifies three electronic states of its diiron center, differing in protonation and bridging ligands. The results reconcile crystallographic heterogeneity and reveal how subtle electronic and structural changes govern non‐heme diiron enzyme reactivity.© 2026 WILEY‐VCH GmbH