Quaternary structure influences the peroxidase activity of peroxiredoxin 3

• Published in: Biochemical and biophysical research communications 2018-03, Vol.497 (2), p.558-563
• Main Authors: Yewdall, N. Amy, Peskin, Alexander V., Hampton, Mark B., Goldstone, David C., Pearce, F. Grant, Gerrard, Juliet A.
• Format: Article
• Language: English
• Subjects: Activity; Cysteine; Peroxiredoxin; Prx3; Quaternary; Structure
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.02.093

Peroxiredoxins are abundant peroxidase enzymes that are key regulators of the cellular redox environment. A major subgroup of these proteins, the typical 2-Cys peroxiredoxins, can switch between dimers and decameric or dodecameric rings, during the catalytic cycle. The necessity of this change in quaternary structure for function as a peroxidase is not fully understood. In order to explore this, human peroxiredoxin 3 (Prx3) protein was engineered to form both obligate dimers (S75E Prx3) and stabilised dodecameric rings (S78C Prx3), uncoupling structural transformations from the catalytic cycle. The obligate dimer, S75E Prx3, retained catalytic activity towards hydrogen peroxide, albeit significantly lower than the wildtype and S78C proteins, suggesting an evolutionary advantage of having higher order self-assemblies. •Mutants created to investigate link between oligomerisation and peroxidase activity.•Obligate dimer is less active than wildtype but still displays peroxidase activity.•2.4 Å structure (PDB: 5UCX) shows cysteine-stabilised protein interface.•Peroxiredoxin oligomerisation into rings optimises peroxidase activity.