The importance of Asn52 in the structure-function relationship of human cytochrome c

The function of the highly conserved residue Asn52 in human cytochrome (H-Cyt ) is not fully understood. Herein, we show that the naturally occurring variant N52S H-Cyt has a perturbed secondary structure, with a small fraction of high-spin species. Remarkably, it exhibits an enhanced peroxidase activity by 3-8-fold at neutral pH, as well as self-oxidation in reaction with H O . This study suggests that the H-bond network mediated by Asn52 is essential to suppress the apoptotic activity of H-Cyt under physiological conditions.