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Mechanism of Glucose Oxidation by Quinoprotein Soluble Glucose Dehydrogenase:  Insights from Molecular Dynamics Studies

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journal contribution
posted on 03.03.2004, 00:00 by Swarnalatha Y. Reddy, Thomas C. Bruice
We have generated 3 ns molecular dynamic (MD) simulations, in aqueous solution, of the bacterial soluble glucose dehydrogenase enzyme·PQQ·glucose complex and intermediates formed in PQQ reduction. In the MD structure of enzyme·PQQ·glucose complex the imidazole of His144 is hydrogen bonded to the hydroxyl hydrogen of H−OC1(H) of glucose. The tightly hydrogen-bonded triad Asp163-His144-glucose (2.70 and 2.91 Å) is involved in proton abstraction from glucose concerted with the hydride transfer from the C1−H of glucose to the >C5O quinone carbon of PQQ. The reaction is assisted by Arg228 hydrogen bonding to the carbonyl oxygen of >C5O. The rearrangement of −(H)C5(O-)−C4(O)− of II to −C5(OH)C4(OH)− of PQQH2 hydroquinone is assisted by general acid protonatation of the >C4O oxygen by protonated His144 and hydrogen bonds of Arg228 to the oxyanion O5. The continuous hydrogen bonding of the amide side chain of Asn229 to >C4O4 oxygen and that of the O5 oxygen of the cofactor to Wat89 is observed throughout the entire reaction.