Dihydroorotase from Methanococcus jannaschii with substrate and product bound

Abstract

Dihydroorotase (DHOase) catalyzes the reversible cyclization of N -carbamoyl-L-aspartate (CA) to L-dihydroorotate (DHO) in the third step of de novo pyrimidine biosy nthesis. Here we report the x - ray structural analysis of DHOase from Methanococcus jannaschii co-crystallized with DHO at pH 6.5. The crystals are isomorphous with the crystals of the apoenzyme (Vitali et al, 2023) with space group P3 221 and a = b = 111.4 Å, c = 101.2 Å. The structure was refined to R = 0.159 and Rfree = 0.176 at a resolution of 1.87 Å. The electron density in the active site corresponds to the average of the substrate (CA) and product (DHO) superimposed, and this is consistent with the reversibility of the reaction.