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dc.contributor.authorMagnusson, Olafur Th.es_ES
dc.contributor.authorToyama, Hirohidees_ES
dc.contributor.authorSaeki, Megumies_ES
dc.contributor.authorRojas, A. M.es_ES
dc.contributor.authorReed, John C.es_ES
dc.contributor.authorLiddington, Robert C.es_ES
dc.contributor.authorKlinman, Judith P.es_ES
dc.contributor.authorSchwarzenbacher, Robertes_ES
dc.date.accessioned2017-07-31T09:38:38Z-
dc.date.available2017-07-31T09:38:38Z-
dc.date.issued2004-
dc.identifier.citationProceedings of the National Academy of Sciences 101(21): 7913–7918 (2004)es_ES
dc.identifier.issn1091-6490-
dc.identifier.urihttp://hdl.handle.net/10261/153718-
dc.description.abstractThe biosynthesis of pyrroloquinoline quinone (PQQ), a vitamin and redox cofactor of quinoprotein dehydrogenases, is facilitated by an unknown pathway that requires the expression of six genes, pqqA to -F. PqqC, the protein encoded by pqqC, catalyzes the final step in the pathway in a reaction that involves ring cyclization and eight-electron oxidation of 3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic-acid to PQQ. Herein, we describe the crystal structures of PqqC and its complex with PQQ and determine the stoichiometry of H2O2 formation and O2 uptake during the reaction. The PqqC structure(s) reveals a compact seven-helix bundle that provides the scaffold for a positively charged active site cavity. Product binding induces a large conformational change, which results in the active site recruitment of amino acid side chains proposed to play key roles in the catalytic mechanism. PqqC is unusual in that it transfers redox equivalents to molecular oxygen without the assistance of a redox active metal or cofactor. The structure of the enzyme-product complex shows additional electron density next to R179 and C5 of PQQ, which can be modeled as O2 or H2O2, indicating a site for oxygen binding. We propose a reaction sequence that involves base-catalyzed cyclization and a series of quinone-quinol tautomerizations that are followed by cycles of O2/H2O2-mediated oxidations. Pyrroloquinoline quinone [4,5-dihydro-4,5-dioxo-1H-pyrrolo-[2,3-f]quinoline-2,7,9-tricarboxylic acid; PQQ (Fig. 1)] is an aromatic, tricyclic ortho-quinone that serves as the redox cofactor for several bacterial dehydrogenases. Among the best known examples are methanol dehydrogenase and glucose dehydrogenase (1, 2). PQQ belongs to the family of quinone cofactors that has been recognized as the third class of redox cofactors following pyridine nucleotide- and flavin-dependent cofactors (3). Although plants and animals do not produce PQQ themselves, PQQ has invoked considerable interest because of its presence in human milk and its remarkable antioxidant properties (4–6). Recently, the first potential eukaryotic PQQ-dependent enzyme [aminoadipic 6-semialdehyde-dehydrogenase (AASDH; U26)] has been identified, indicating that PQQ may function as a vitamin in mammals as well (7).es_ES
dc.description.sponsorshipR.S. was supported by Austrian Science Fund Fellowship J2209-B04, J.P.K. by National Institutes of Health Grant GM39296, and O.T.M. by a postdoctoral fellowship from the Miller Institute for Basic Research in Science, University of California, Berkeley.es_ES
dc.language.isoenges_ES
dc.publisherNational Academy of Sciences (U.S.)es_ES
dc.rightsclosedAccesses_ES
dc.titleQuinone biogenesis: Structure and mechanism of PqqC, the final catalyst in the production of pyrroloquinoline quinonees_ES
dc.typeartículoes_ES
dc.identifier.doi10.1073/pnas.0402640101-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://doi.org/10.1073/pnas.0402640101es_ES
dc.contributor.funderAustrian Science Fundes_ES
dc.contributor.funderNational Institutes of Health (US)es_ES
dc.contributor.funderUniversity of Californiaes_ES
dc.relation.csicNoes_ES
oprm.item.hasRevisionno ko 0 false*
dc.identifier.funderhttp://dx.doi.org/10.13039/501100002428es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100000002es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100005595es_ES
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