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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

The structure of a native L-amino acid oxidase, the major component of the Vipera ammodytes ammodytes venomic, reveals dynamic active site and quaternary structure stabilization by divalent ions

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Autor(es):
Georgieva, Dessislava [1, 2] ; Murakami, Mario [3] ; Perband, Markus [1, 4] ; Arni, Raghuvir [5] ; Betzel, Christian [1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Hamburg, Inst Biochem & Mol Biol, Lab Struct Biol Infect & Inflammat, DESY, D-22603 Hamburg - Germany
[2] Bulgarian Acad Sci, Inst Organ Chem, BU-1113 Sofia - Bulgaria
[3] Natl Ctr Res Energy & Mat, Natl Lab Biosci, BR-13083970 Campinas, SP - Brazil
[4] Univ Med Ctr, Inst Med Microbiol Virol & Hyg, D-20246 Hamburg - Germany
[5] IBILCE UNESP, Dept Phys, Sao Jose Do Rio Preto, SP - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: MOLECULAR BIOSYSTEMS; v. 7, n. 2, p. 379-384, 2011.
Citações Web of Science: 15
Resumo

The 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 Zn(2+) 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. (AU)

Processo FAPESP: 07/54865-1 - Applied venom (proteômica aplicada de venenos)
Beneficiário:Raghuvir Krishnaswamy Arni
Modalidade de apoio: Auxílio à Pesquisa - Regular