Crystal structure of human α-lactalbumin at 1·7 Å resolution

The three-dimensional X-ray structure of human α-lactalbumin, an important component of milk, has been determined at 1·7 Å (0·17 nm) resolution by the method of molecular replacement, using the refined structure of baboon α-lactalbumin as the model structure. The two proteins are known to have more than 90% amino acid sequence identity and crystallize in the same orthorhombic space group, P2₁2₁2. The crystallographic refinement of the structure using the simulated annealing method, resulted in a crystallographic R-factor of 0·209 for the 11,373 observed reflections (F ≥ 2σ(F)) between 8 and 1·7 Å resolution. The model comprises 983 protein atoms, 90 solvent atoms and a bound calcium ion. In the final model, the root-mean-square deviations from ideality are 0·013 Å for covalent bond distances and 2·9° for bond angles. Superposition of the human and baboon α-lactalbumin structures yields a root-mean-square difference of 0·67 Å for the 123 structurally equivalent C^α atoms. The C terminus is flexible in the human α-lactalbumin molecule. The striking structural resemblance between α-lactalbumins and C-type lysozymes emphasizes the homologous evolutionary relationship between these two classes of proteins.