Ullah, A. [UNESP]Souza, T. A C BAbrego, J. R B [UNESP]Betzel, C.Murakami, M. T.Arni, R. K. [UNESP]2014-05-272014-05-272012-04-27Biochemical and Biophysical Research Communications, v. 421, n. 1, p. 124-128, 2012.0006-291X1090-2104http://hdl.handle.net/11449/73296l-Amino acid oxidases (LAAOs) are flavoenzymes that catalytically deaminate l-amino acids to corresponding α-keto acids with the concomitant production of ammonia (NH 3) and hydrogen peroxide (H 2O 2). Particularly, snake venom LAAOs have been attracted much attention due to their diverse clinical and biological effects, interfering on human coagulation factors and being cytotoxic against some pathogenic bacteria and Leishmania ssp. In this work, a new LAAO from Bothrops jararacussu venom (BjsuLAAO) was purified, functionally characterized and its structure determined by X-ray crystallography at 3.1å resolution. BjsuLAAO showed high catalytic specificity for aromatic and aliphatic large side-chain amino acids. Comparative structural analysis with prokaryotic LAAOs, which exhibit low specificity, indicates the importance of the active-site volume in modulating enzyme selectivity. Surprisingly, the flavin adenine dinucleotide (FAD) cofactor was found in a different orientation canonically described for both prokaryotic and eukaryotic LAAOs. In this new conformational state, the adenosyl group is flipped towards the 62-71 loop, being stabilized by several hydrogen-bond interactions, which is equally stable to the classical binding mode. © 2012 Elsevier Inc.124-128engAmino acid specificityBothrops jararacussuCrystal structureFAD-binding modeL-Amino acid oxidaseamino acid oxidasesnake venomcrystal structurecrystallizationenzyme active siteenzyme purificationenzyme specificityenzyme structureenzyme substratehydrogen bondhydrophobicitymolecular interactionnonhumanpriority journalstructure analysisAmino Acid SequenceAnimalsBothropsCrotalid VenomsCrystallography, X-RayEnzyme StabilityHydrophobic and Hydrophilic InteractionsL-Amino Acid OxidaseMolecular Sequence DataProtein Structure, SecondaryEukaryotaProkaryotaArtigo10.1016/j.bbrc.2012.03.129Acesso aberto2-s2.0-848603256472-s2.0-84860325647.pdf91625089789458870000-0003-2460-1145