Mapping the Exit Route of Hydrogen Peroxide From the Manganese Superoxide Dismutase (MnSOD) Active Site.

ABSTRACT: Mitochondrial manganese superoxide dismutase (MnSOD) converts superoxide (O₂ ^●-) into hydrogen peroxide (H₂O₂) and molecular oxygen (O₂), serving as a key defense against oxidative damage. Despite decades of research, the product exit pathway in MnSOD remains understudied, due to the enzyme's rapid, diffusion-limited catalysis. Here, we structurally characterize the H₂O₂ exit route in MnSOD, using a kinetically impaired Gln143Asn variant. In the wild-type enzyme, Gln143 participates in proton transfer reactions with the Mn³⁺-bound solvent (WAT1) to drive redox cycling of the metal for effective O₂ ^●- dismutation. Substitution with Asn disrupts the proton transfer, as Asn is too far

SUBMITTER: Dasgupta M 

PROVIDER: S-EPMC12338682 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature