ahpF

AhpF, short for alkyl hydroperoxide reductase subunit F, is a flavoprotein component of the bacterial alkyl hydroperoxide reductase (AhpCF) system. It serves as the electron donor that regenerates the active, reduced form of the peroxiredoxin AhpC, enabling continued detoxification of peroxides.

Biochemical function: In the AhpCF system, AhpF contains a flavin adenine dinucleotide (FAD) cofactor and a redox-active disulfide. Electrons are donated from NADH to the FAD cofactor in AhpF, and are then transferred through internal redox centers to AhpC. AhpC, after reducing a peroxide substrate such as hydrogen peroxide or organic hydroperoxides, becomes oxidized and is subsequently re-reduced by AhpF, restoring its activity for additional rounds of peroxide reduction.

Structure and domain organization: AhpF is typically a flavoprotein disulfide reductase that may function as a monomer or dimer, depending on the organism. It possesses an N-terminal domain that binds FAD and a C-terminal region that harbors the redox-active disulfide necessary for transferring electrons to AhpC.

Genetic context and distribution: The ahpF gene is commonly found in operons with ahpC, forming the ahpCF gene pair in many bacteria. The AhpCF system is widespread among Gram-negative bacteria and is present in some Gram-positive species, contributing to defense against oxidative stress in aerobic environments.

Biological significance: By fueling the reduction cycle of AhpC, AhpF plays a key role in protecting cells from oxidative damage caused by hydrogen peroxide and organic hydroperoxides. This system complements other antioxidant defenses, such as catalases and additional peroxidases, and can influence bacterial fitness and pathogenicity in certain contexts.