The incorporation of a non-natural amino acid (aza-tryptophan) may help to crystallize a protein and to solve its crystal structure. Application to ­bacteriophage λ lysozyme.

Until now, wild-type bacteriophage λ lysozyme had been impossible to crystallize. This difficulty could be overcome by the replacement of the four tryptophan residues by aza-tryptophans. Analysis of the intermolecular and intramolecular contacts in this modification allows understanding of the differences in behaviour between the native and modified molecules. Furthermore, this mutation was very useful for the creation of new heavy-atom binding sites and for the solution of the non-crystallographic symmetry, which is extremely important for phase improvement. This procedure seems to be generally applicable, at least in the search for new possibilities for heavy-atom binding sites.