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Unexpected Electron Spin Density on the Axial Methionine Ligand in CuA Suggests Its Involvement in Electron Pathways

submitted on 14.11.2019, 01:27 and posted on 25.11.2019, 16:14 by Marcos N. Morgada, María-Eugenia Llases, Estefania Giannini, María Ana Castro, Pedro M. Alzari, Daniel H. Murgida, María-Natalia Lisa, Alejandro J. Vila

The CuA center is a paradigm for the study of long-range biological electron transfer. This metal center is an essential cofactor for terminal oxidases like Cytochrome c oxidase, the enzymatic complex responsible for cellular respiration in eukaryotes and in most bacteria. CuA acts as an electron hub by transferring electrons from reduced cytochrome c to the catalytic site of the enzyme where dioxygen reduction takes place. Different electron transfer pathways have been proposed involving a weak axial methionine ligand residue, conserved in all CuA sites. This hypothesis has been challenged by theoretical calculations indicating the lack of electron spin density in this ligand. Here we report an NMR study with selectively labeled methionine in a native CuA. NMR spectroscopy discloses the presence of net electron spin density in the methionine axial ligand in the two alternative ground states of this metal center. Similar spin delocalization observed on two second sphere mutants further supports this evidence. These data provide a novel view of the electronic structure of CuA centers and support previously neglected electron transfer pathways.


Argentina-France ECOS exchange program (ECOS A15B01)

Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT, PICT 2012-1285)


Email Address of Submitting Author


Instituto de Biologia Molecular y Celular de Rosario - Universidad Nacional de Rosario



ORCID For Submitting Author


Declaration of Conflict of Interest

There are no conflicts to declare