Issue 2, 2011

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

Abstract

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 Å 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.

Graphical abstract: 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

Article information

Article type
Paper
Submitted
13 Jul 2010
Accepted
13 Sep 2010
First published
11 Oct 2010

Mol. BioSyst., 2011,7, 379-384

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

D. Georgieva, M. Murakami, M. Perband, R. Arni and C. Betzel, Mol. BioSyst., 2011, 7, 379 DOI: 10.1039/C0MB00101E

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