Pyroccocus furiosus rubredoxin (PFRD), like most studied hyperthermophilic proteins, does not undergo reversible folding. The irreversibility of folding is thought to involve PFRD's iron-binding site. Here we report a PFRD variant (PFRD-XC4) whose iron binding site was redesigned to eliminate iron binding using a computational design algorithm. PFRD-XC4 folds without iron and exhibits reversible folding with a melting temperature of 82 degrees C, a thermodynamic stability of 3.2 kcal mol(-1) at 1 degrees C, and NMR chemical shifts similar to that of the wild-type protein. This variant should provide a tractable model system for studying the thermodynamic origins of protein hyperthermostability.