Quinoprotein methanol dehydrogenase: a molecular dynamics study and comparison with crystal structure

Abstract One of the mechanisms proposed for methanol oxidation by methanol dehydrogenase (MDH) involves a hydride transfer to the quinone carbonyl carbon C5 of 2,7,9-tricarboxy-1H-pyrrolo[2,3-f]-quinoline-4,5-dione (PQQ), initiated by abstraction of a proton from the substrate methanol by a general base. Molecular dynamics studies are performed on MDH-bound to the C5 reduced intermediate (C5RI) of PQQ, for 3 ns. The structural features of the MD and X-ray structures are compared. An interesting feature observed during simulations is the strong hydrogen bond between oxyanion O5 of C5RI and Asp297–CO 2 H in the active site. Asp297–CO 2 − is suggested to be the general-base catalyst for removing the hydroxyl proton of methanol in concert with the hydride ion transfer from the putative methoxide to C5 carbonyl of PQQ. The formed Asp297–CO 2 H acts as the required proton source for the immediate product. Anticorreleated motions observed in the MD structure are not across the active site to influence the reaction mechanism of MDH.