Lanthanides-based catalysis in eukaryotes

Abstract

Rare earth elements play a pivotal role in high-technology devices, are used as contrast agents for magnetic resonance imaging in clinical settings, are explored as drug carriers for tumor photodynamic therapy, and are used as fertilizers. From the biochemical viewpoint, they act not only as antagonists of Ca²⁺ but have been proposed as alternative to Ca²⁺ in metallo-enzymes, in particular in Ce³⁺ -based methanol dehydrogenases (MDHs). Up to now, the analysis of protein sequence databases identified Ce³⁺ -based MHDs only in Archea and Bacteria. Here, we report evidence that Ce³⁺ -based MDHs are also present in higher organisms. These enzymes, identified in the parasite Plasmodium yoelii yoelii, in the spider Nephila clavipes, in the Tibetan antelope Pantholops hodgsonii, and in Homo sapiens, are encoded by intronless genes, thus representing a case of multiple, independent lateral gene transfer from Prokaryotes to Eukaryotes. The conservation of residues involved in the Ce³⁺ coordination, pyrroquinoline quinone cofactor recognition and in the structure stabilization suggests that these enzymes belong to the Ce³⁺ -dependent MDH family, hitherto considered as exclusive of Prokaryotes. © 2018 IUBMB Life, 70(11):1067-1075, 2018.

Keywords: Ca2+-dependent methanol dehydrogenase; Ce3+-dependent methanol dehydrogenase; evolution; lanthanides-based catalysis; lateral gene transfer; structure.