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Publication Abstract from PubMed

Human manganese superoxide dismutase (MnSOD) is a crucial oxidoreductase that maintains the vitality of mitochondria by converting O (2) (●-) to O (2) and H (2) O (2) with proton-coupled electron transfers (PCETs). Since changes in mitochondrial H (2) O (2) concentrations are capable of stimulating apoptotic signaling pathways, human MnSOD has evolutionarily gained the ability to be highly inhibited by its own product, H (2) O (2) . A separate set of PCETs is thought to regulate product inhibition, though mechanisms of PCETs are typically unknown due to difficulties in detecting the protonation states of specific residues that coincide with the electronic state of the redox center. To shed light on the underlying mechanism, we combined neutron diffraction and X-ray absorption spectroscopy of the product-bound, trivalent, and divalent states to reveal the all-atom structures and electronic configuration of the metal. The data identifies the product-inhibited complex for the first time and a PCET mechanism of inhibition is constructed.

Revealing the atomic and electronic mechanism of human manganese superoxide dismutase product inhibition.,Azadmanesh J, Slobodnik K, Struble LR, Lutz WE, Coates L, Weiss KL, Myles DAA, Kroll T, Borgstahl GEO bioRxiv [Preprint]. 2024 Jan 27:2024.01.26.577433. doi: , 10.1101/2024.01.26.577433. PMID:38328249^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.