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Preferential Binding of Lanthanides to Methanol Dehydrogenase Evaluated with Density Functional Theory.


ABSTRACT: Methanol dehydrogenase (MDH) is an enzyme used by certain bacteria for the oxidation of methanol to formaldehyde, which is a necessary metabolic reaction. The discovery of a lanthanide-dependent MDH reveals that lanthanide ions (Ln3+) have a role in biology. Two types of MDH exist in methane-utilizing bacteria: one that is Ca2+-dependent (MxaF) and another that is Ln3+-dependent. Given that the triply charged Ln3+ are strongly hydrated, it is not clear how preference for Ln3+ is manifested and if the Ca2+-dependent MxaF protein can also bind Ln3+ ions. A computational approach was used to estimate the Gibbs energy differences between the binding of Ln3+ and Ca2+ to MDH using density functional theory. The results show that both proteins bind La3+ with higher affinity than Ca2+, albeit with a more pronounced difference in the case of Ln3+-dependent MDH. Interestingly, the binding of heavier lanthanides is preferred over the binding of La3+, with Gd3+ showing the highest affinity for both proteins of all Ln3+ ions that were tested (La3+, Sm3+, Gd3+, Dy3+, and Lu3+). Energy decomposition analysis reveals that the higher affinity of La3+ than Ca2+ to MDH is due to stronger contributions of electrostatics and polarization, which overcome the high cost of desolvating the ion.

SUBMITTER: Friedman R 

PROVIDER: S-EPMC8028316 | biostudies-literature |

REPOSITORIES: biostudies-literature

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