2OLN

NikD is an unusual amino acid oxidising enzyme that contains covalently bound FAD and catalyses a 4-electron oxidation of piperideine-2-carboxylic acid to picolinate and plays a critical role in the biosynthesis of nikkomycin antibiotics. Nikkomycins are potent antifungal agents that block cell wall formation by inhibiting the biosynthesis of chitin, the second most abundant polysaccharide in nature.

NikD exhibits two unique structural features as compared with other members of the MSOX family of amino acid oxidases:

1. nikD contains a mobile cation-binding loop of unknown function that has been shown to bind sodium or potassium ions.
2. nikD exhibits two distinct modes for substrate binding, as judged by the open and closed forms of the enzymeˇ¤picolinate complex. In the closed form, picolinate is bound parallel with the flavin ring, the indole ring of Trp355 is perpendicular to the flavin ring, and the active site is inaccessible to solvent. This ligand binding mode is compatible with redox catalysis and similar to that observed with MSOX. In the open form, picolinate is bound perpendicular to the flavin ring, Trp355 is stacked atop the flavin ring, and the active site is accessible to solvent. This binding mode is not compatible with redox catalysis or observed with MSOX. However, the coplanar orientation of the flavin and indole rings is required for charge-transfer interaction between FAD and Trp355, a feature observed with solutions of the ligand-free enzyme at weakly alkaline pH