Crystal structure of 1′-OH-carotenoid 3,4-desaturase from Nonlabens dokdonensis DSW-6
•We determined a crystal structure of γ-carotenoid desaturase from Nonlabens dokdonensis (DdCrtD).•FAD cofactor binding mode was elucidated.•A long and hydrophobic substrate binding tunnel for the 1′-OH-γ-carotenoid substrate was revealed.
The γ-carotenoids, such as myxol and saproxanthin, have a high potential to be utilized in nutraceutical and pharmaceutical industries for their neuro-protective and antioxidant effects. CrtD is involved in the production of γ-carotenoids by desaturating the C3′–C4′ position of 1′-OH-γ-carotenoid. We determined the crystal structure of CrtD from Nonlabens dokdonensis DSW-6 (NdCrtD), the first structure of CrtD family enzymes. The NdCrtD structure was composed of two distinct domains, an FAD-binding domain and a substrate-binding domain, and the substrate-binding domain can be divided into two subdomains, a Rossmann fold-like subdomain and a lid subdomain. Although the FAD-binding domain showed a structure similar to canonical FAD-containing enzymes, the substrate-binding domain exhibited a novel structure to constitute a long and hydrophobic tunnel with a length of ∼40 Å. The molecular docking-simulation reveals that the tunnel provides an appropriate substrate-binding site for the carotenoid such as 1′-OH-γ-carotene with a length of ∼35 Å. We could predict residues related to recognize the 1′-hydroxyl group and to stabilize the hydrophobic end without hydroxyl group. Moreover, we suggest that the flexible entrance loop may undergo an open–closed formational change during the binding of the substrate.
Journal: Enzyme and Microbial Technology - Volume 77, September 2015, Pages 29–37