title: Conformation of coenzyme pyrroloquinoline quinone and role of Ca2+ in the catalytic mechanism of quinoprotein methanol dehydrogenase.
abstract: The ab initio structures of 2,7,9-tricarboxypyrroloquinoline quinone (PQQ), semiquinone (PQQH), and dihydroquinone (PQQH2) have been determined and compared with ab initio structures of the (PQQ)Ca2+, (PQQH)Ca2+, and (PQQH2)Ca2+ complexes as well as the x-ray structure of (PQQ)Ca2+ bound at the active site of the methanol dehydrogenase (MDH) of methyltropic bacteria. Plausible mechanisms for the MDH oxidation of methanol involving the (PQQ)Ca2+ complex are explored via ab initio computations and discussed. Considering the reaction of methanol with PQQ in the absence of Ca2+, nucleophilic addition of methanol to the PQQ C-5 carbonyl followed by a retro-ene elimination is deemed unlikely due to large energy barrier. A much more favorable disposition of the methanol C-5 adduct to provide formaldehyde involves proton ionization of the intermediate followed by elimination of methoxide concerted with hydride transfer to the oxygen of the C-4 carbonyl. Much the same transition state is reached if one searches for the transition state beginning with Asp-303-CO2-general-base removal of the methanol proton of the (PQQ)Ca2+O(H)CH3 complex concerted with hydride transfer to the oxygen at C-4. For such a mechanism the role of the Ca2+ moiety would be to (i) contribute to the formation of the ES complex (ii) provide a modest decrease in the pKa of methanol substrate,; and (iii) polarize the oxygen at C-5.
authors.affiliation: Department of Chemistry, University of California, Santa Barbara, CA 93106, USA.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Zheng
authors.forename: T C
authors.initials: TC
authors.lastname: Bruice
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D002384:Catalysis; D003198:Computer Simulation; D000432:Methanol / Q000737:chemistry / Q000378:metabolism*; D008772:Methylococcaceae / Q000201:enzymology; D008956:Models, Chemical; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D045542:PQQ Cofactor; D015363:Quinolones / Q000737:chemistry / Q000378:metabolism*; D011809:Quinones / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015363:Quinolones; D011809:Quinones; D045542:PQQ Cofactor; D000429:Alcohol Oxidoreductases; C019641:alcohol dehydrogenase (acceptor); D002118:Calcium; D000432:Methanol