Iron–Sulfur Clusters Coordinated by Four Conserved Cysteine Residues in Proteins: Structural Diversity and Redox Function

Abstract

Protein‐bound iron–sulfur ([Fe–S]) clusters are ubiquitous and structurally diverse cofactors in biological systems, performing a wide range of biochemical functions. These [Fe–S] clusters are most commonly coordinated by cysteine residues, within defined protein scaffolds, which modulate their structural organization and redox behavior. Therefore, this review focuses on iron–sulfur cofactors ligated by four cysteine residues with variable spacing, which give rise to distinct [Fe–S] cofactors within protein scaffolds such as [1Fe] rubredoxins (Rds) and [2Fe–2S]‐/[4Fe–4S]‐ferredoxins (Fds), emphasizing the magnetic behaviors and a wide spectrum of redox potentials governed by diverse structural and environmental factors. In addition, the review highlights the structural versatility of nonclassical [Fe–S] clusters in proteins and their diverse biological roles.