Georgieva, DessislavaMurakami, MarioPerband, MarkusArni, Raghuvir [UNESP]Betzel, Christian2014-05-202014-05-202011-01-01Molecular Biosystems. Cambridge: Royal Soc Chemistry, v. 7, n. 2, p. 379-384, 2011.1742-206Xhttp://hdl.handle.net/11449/22066The crystal structure of the major component of the Vipera ammodytes ammodytes venomic, a flavotoxin, member of the L-amino acid oxidase (LAAO) family, has been determined and refined at 2.6 angstrom resolution. The asymmetric unit consists of four molecules, each bound to oxidized FAD, representing a dimer of dimers. The binding of four Zn2+ ions stabilizes the enzymatically active quaternary structure and is considered important for the biological activity of LAAO and other flavoproteins. Each monomer consists of three domains with a cofactor bound between the FAD and substrate binding domains, and a solvent exposed glycosylation site which is considered crucial for the toxicity. Comparison of LAAO structures in the absence and presence of a substrate indicates conformational changes in the dynamic active site. The active site H-bond network involving the triad Lys326-Water-N5 of FAD is formed only upon substrate binding, and results in the increased mobility of the isoalloxazine system. Details of the catalytic transformation of amino acid substrates are discussed.379-384engArtigo10.1039/c0mb00101eWOS:000286390600011Acesso restrito91625089789458870000-0003-2460-1145