Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
The crystal structure of the enzyme Dicer from Giardia intestinalis was solved to 3.3 A resolution by MAD using crystals belonging to space group P2(1)2(1)2 [Macrae et al. (2006), Science, 311, 195-198]. These crystals were derived from crystals that diffracted X-rays to 3.0 A 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 P4(1) 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.