An unusual case of pseudo-merohedral twinning in orthorhombic crystals of Dicer

The crystal structure of the enzyme Dicer from Giardia intestinalis was solved to 3.3 Å resolution by MAD using crystals belonging to space group P2₁2₁2 [Macrae et al. (2006), Science, 311, 195-198]. These crystals were derived from crystals that diffracted X-rays to 3.0 Å resolution but were refractory to structure determination because they were twinned. It is shown here that the original Dicer crystals represent an unusual case of perfect pseudo-merohedral twinning of orthorhombic crystals. Before the twinning problem was overcome, it was possible to calculate a low-resolution electron-density map in space group P4₁ that was used to build a partial molecular model. Experimental phases were sufficient to identify heavy-atom sites that indicated space-group inconsistency, leading to identification of the true space group. This information guided the search for different crystallization conditions that yielded untwinned crystals and ultimately a fully interpretable electron-density map.