Snake venom L-amino acid oxidases: trends in pharmacology and biochemistry

Abstract

L-amino acid oxidases are enzymes found in several organisms, including venoms of snakes, where they contribute to the toxicity of ophidian envenomation. Their toxicity is primarily due to enzymatic activity, but other mechanisms have been proposed recently which require further investigation. L-amino acid oxidases exert biological and pharmacological effects, including actions on platelet aggregation and the induction of apoptosis, hemorrhage, and cytotoxicity. These proteins present a high biotechnological potential for the development of antimicrobial, antitumor, and antiprotozoan agents. This review provides an overview of the biochemical properties and pharmacological effects of snake venom L-amino acid oxidases, their structure/activity relationship, and supposed mechanisms of action described so far.

Figure 1

Mechanism of chemical reaction catalyzed by L-amino acid oxidases (LAAOs) [37].

Figure 2

Sequence alignment of L-amino acid oxidases from snake venoms of some regions of the world. The alignment was performed using the program ClustalW [101]. Only nonconserved amino acids are showed.

Figure 3

Phylogenetic representation of amino acid sequence alignments of L-amino acid oxidases from snake venoms of some regions of the world. Trees were obtained as described in the Methods section at http://www.phylogeny.fr/. Numbers close to the nodes represent the support value for each branch. The region of the world is shown after the accession numbers. The sequence gi|327266254_Anolis_Root_Tree is the root control of the tree.

Figure 4

Structure of LAAO from Calloselasma rhodostoma (PDB code 2IID) with a resolution of 1.80 Å [50]. The structure was shown in ribbon representation using Swiss-PDBViewer software with renderization POV-ray [104]. In blue is the α-helical domain, in red is the substrate-binding domain, and in green is the FAD-binding domain.