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

Autor(es)

Georgieva, Dessislava ^{[1, 2]} ; Murakami, Mario ^[3] ; Perband, Markus ^{[1, 4]} ; Arni, Raghuvir ^[5] ; Betzel, Christian ^[1]

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

• 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