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Direct Detection of Coupled Proton and Electron Transfers in Human Manganese Superoxide Dismutase

Portrait of speaker, Prof. Gloria Borgstahl
Prof. Gloria Borgstahl
University of Nebraska Medical Center
iSTEM-2 Building, Room 1218
Inorganic Seminar

Human manganese superoxide dismutase is a critical oxidoreductase found in the mitochondrial matrix. Concerted proton and electron transfers are used by the enzyme to rid the mitochondria of O2•−. The mechanisms of concerted transfer enzymes are typically unknown due to the difficulties in detecting the protonation states of specific residues and solvent molecules at particular redox states. Here, neutron diffraction of two redox-controlled manganese superoxide dismutase crystals reveal the all-atom structures of Mn3+ and Mn2+ enzyme forms. The structures deliver direct data on protonation changes between oxidation states of the metal. Observations include glutamine deprotonation, the involvement of tyrosine and histidine with altered pKas, and four unusual strong-short hydrogen bonds, including a low barrier hydrogen bond. We report a concerted proton and electron transfer mechanism for human manganese superoxide dismutase from the direct visualization of active site protons in Mn3+ and Mn2+ redox states.



Azadmanesh, J., Trickel, S. R., Weiss, K.L., Coates, L. and Borgstahl, G. E. O.  “Neutron diffraction analysis of human manganese superoxide dismutase” Acta Crystallogr. F73, 235-240 (2017).

Azadmanesh, J., Trickel, S. R., and Borgstahl, G. E. O.  “Substrate-analog binding sites and electrostatic surfaces of human manganese superoxide dismutase” J. Struct. Biol. 199, 68-75 (2017).

Azadmanesh, J., Lutz, W. E., Weiss, K. L., Coates, L. and Borgstahl, G. E. O. “Redox manipulation of the manganese metal in human manganese superoxide dismutase for neutron diffractionActa Crystallogr. F74, 677-687 (2018)

Azadmanesh, J., Lutz, W.E., Coates L., Weiss, K. and Borgstahl, G. E. O. “Direct detection of coupled proton and electron transfers in human manganese superoxide dismutase” Nature Communications 12:2079 (2021).

Azadmanesh, J., Lutz, W.E., Coates, L., Weiss, K.L. and Borgstahl, G. E. O.Cryotrapping peroxide in the active site of human mitochondrial manganese superoxide dismutase crystals for neutron diffraction” Acta Crystallogr. F78, 8-16 (2022).

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