The structure of L-amino acid oxidase reveals the substrate trajectory into an enantiomerically conserved active site

The structure of L-amino acid oxidase (LAAO) from Calloselasma rhodostoma h as been determined to 2.0 Angstrom resolution in the presence of two ligand s: citrate and o-aminobenzoate (AB), The protomer consists of three domains : an FAD-binding domain, a substrate-binding domain and a helical domain. T he interface between the substrate-binding and helical domains forms a 25 A ngstrom long funnel, which provides access to the active site. Three AB mol ecules are visible within the funnel of the LAAO-AB complex; their orientat ions suggest the trajectory of the substrate to the active site. The innerm ost AB molecule makes hydrogen bond contacts with the active site residues, Arg90 and Gly464, and the aromatic portion of the ligand is situated in a hydrophobic pocket. These contacts are proposed to mimic those of the natur al substrate. Comparison of LAAO with the structure of mammalian D-amino ac id oxidase reveals significant differences in their modes of substrate entr y. Furthermore, a mirror-symmetrical relationship between the two substrate -binding sites is observed which facilitates enantiomeric selectivity while preserving a common arrangement of the atoms involved in catalysis.