How Can Methanol Dehydrogenase from Methylacidiphilum fumariolicum Work with the Alien CeIII Ion in the Active Center? A Theoretical Study

5 years ago

How Can Methanol Dehydrogenase from Methylacidiphilum fumariolicum Work with the Alien CeIII Ion in the Active Center? A Theoretical Study

Tiziana Marino, Nino Russo, Mario Prejanò

Lanthanides are an example of nonbiogenic metal species and have been widely used in crystallographic and spectroscopic studies to probe Mg2+/Ca2+ binding sites in metalloproteins by replacing the native cofactor. Recently, a methanol dehydrogenase (MDH) enzyme containing cerium ion in the active site has been isolated from Methylacidiphilum fumariolicum bacterium. With the aim to highlight as metal ion substitution can be reflected in catalytic mechanism, a comparative DFT study between Ca- and Ce-MDH has been undertaken. The obtained potential energy surfaces (PES), for two considered reaction mechanisms (named A and B), indicate mechanism A (addition-elimination and protonation processes) as the favored for both the enzymes and show as the barrier for the rate-determining step of Ce-MDH requires 19.4 kcal mol−1. Ca- vs. Ce-methanol dehydrogenase (MDH): From the comparison with Ca-MDH, it emerges that although the reaction mechanism is the same, the presence of CeIII center favors the formation of the nucleophilic agent and the first produced intermediate is thermodynamically stabilized in Ce-MDH. This result provides the explanation for the different potential energy surface behaviors in the next addition and elimination steps.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201700381