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Publication Abstract from PubMed

Enzymes that catalyze long-range electron transfer (ET) reactions often function as higher order complexes that possess two structurally symmetrical halves. The functional advantages for such an architecture remain a mystery. Using cryoelectron microscopy we capture snapshots of the nitrogenase-like dark-operative protochlorophyllide oxidoreductase (DPOR) during substrate binding and turnover. DPOR catalyzes reduction of the C17 = C18 double bond in protochlorophyllide during the dark chlorophyll biosynthetic pathway. DPOR is composed of electron donor (L-protein) and acceptor (NB-protein) component proteins that transiently form a complex in the presence of ATP to facilitate ET. NB-protein is an alpha(2)beta(2) heterotetramer with two structurally identical halves. However, our structures reveal that NB-protein becomes functionally asymmetric upon substrate binding. Asymmetry results in allosteric inhibition of L-protein engagement and ET in one half. Residues that form a conduit for ET are aligned in one half while misaligned in the other. An ATP hydrolysis-coupled conformational switch is triggered once ET is accomplished in one half. These structural changes are then relayed to the other half through a di-nuclear copper center at the tetrameric interface of the NB-protein and leads to activation of ET and substrate reduction. These findings provide a mechanistic blueprint for regulation of long-range electron transfer reactions.

Cryo-EM captures the coordination of asymmetric electron transfer through a di-copper site in DPOR.,Kashyap R, Walsh N, Deveryshetty J, Tokmina-Lukaszewska M, Zhao K, Gan YJ, Hoffman BM, Sarangi R, Bothner B, Bennett B, Antony E Nat Commun. 2025 Apr 24;16(1):3866. doi: 10.1038/s41467-025-59158-7. PMID:40274796^[1]

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