Simulation of the Enzymatic Reaction of Dogfish M_4 Lactate Dehydrogenase : A Molecular Orbital Study on the Reactivity of Pyruvate

概要

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Simulation of the enzymatic reaction of dogfish M_4 lactate dehydrogenase (LDH) was performed. In the enzymatic reaction from L-lactate to pyruvate, the structure in which the proton transfer from L-lactate to His 195 is coupled with the hydride transfer from L-lactate to NAD^+ was simulated. In the reverse reaction, the structure in which the proton transfer from His 195 to pyruvate is coupled with the hydride transfer from NADH to pyruvate was also simulated. Since the proton of His 195 approaches the carbonyl oxygen of pyruvate from the π direction of the pyruvate plane in the simulation, the electronic structure and the reactivity of pyruvate were studied from a quantum chemical point of view, using the ab initio LCAO MO method. When the carbonyl carbon of pyruvate is attacked by the hydride ion of NADH, the total π electron density of the carbonyl oxygen of pyruvate increases substantially. Therefore, the proton of His 195 attacks the carbonyl oxygen of pyruvate from the π direction. Moreover, the pyruvate-Arg 171 complex having two nearly parallel hydrogen bonds is more easily attacked by hydride than complexes having other conformations.
社団法人日本薬学会の論文
1980-10-25