title: Quantum chemical modeling of methanol oxidation mechanisms by methanol dehydrogenase enzyme: effect of substitution of calcium by barium in the active site.
abstract: Previous experimental studies have shown that the activation energy for methanol oxidation by naturally occurring Ca(2+)-containing methanol dehydrogenase (MDH) enzyme is double the methanol activation energy by Ba(2+)-MDH. However, neither the reason for this difference nor the specific transition states and intermediates involved during the methanol oxidation by Ba(2+)-MDH have been clearly stated. Hence, an MDH active site model based on the well-documented X-ray crystallographic structure of Ca(2+)-MDH is selected, where the Ca(2+) is replaced by a Ba(2+) ion at the active site center, and the addition-elimination (A-E) and hydride-transfer (H-T) methanol oxidation mechanisms, already proposed in the literature for Ca(2+)-MDH, are tested for Ba(2+)-MDH at the BLYP/DNP theory level. Changes in the geometries and energy barriers for all the steps are identified, and qualitatively, similar (when compared to Ca(2+)-MDH) intermediates and transition states associated with each step of the mechanisms are found in the case of Ba(2+)-MDH. For both the A-E and H-T mechanisms, almost all the free-energy barriers associated with all of the steps are reduced in the presence of Ba(2+)-MDH, and they are kinetically feasible. The free energy barriers for methanol oxidation by Ba(2+)-MDH, particularly for the rate-limiting steps of both mechanisms, are almost half the corresponding barriers calculated for the case of Ca(2+)-MDH, which is in agreement with experimental observations.
authors.affiliation: Institute for Micromanufacturing, Chemical Engineering Program, Louisiana Tech University, Ruston, Louisiana 71272, USA.
authors.forename: Nagesh B
authors.initials: NB
authors.lastname: Idupulapati
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Mainardi
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000187:drug effects; D001464:Barium / Q000737:chemistry* / Q000494:pharmacology; D002118:Calcium / Q000737:chemistry* / Q000494:pharmacology; D020134:Catalytic Domain / Q000187:drug effects; D018360:Crystallography, X-Ray; D000432:Methanol / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D010084:Oxidation-Reduction; D011789:Quantum Theory
chemical_list: D001464:Barium; D000429:Alcohol Oxidoreductases; C019641:alcohol dehydrogenase (acceptor); D002118:Calcium; D000432:Methanol