(A) Overview of all molecules that the C-lobe of molecule A contacts in the context of the crystal lattice. The symmetry operations that ought to be applied in order to obtain the respective interface (specified in fractional space relative to the structure position in the PDB file) are provided. (B–D) Details of each lattice interface that the C-lobe of molecule A is involved in. The interface area (difference in the total accessible surface areas of the isolated and interfacing structures divided by 2) and the solvation free energy gain upon formation of the interface, ΔiG, (difference in the total solvation energies of the isolated and the interfacing structures) were calculated with PISA (Krissinel and Henrick, 2007). In (B) residues that form hydrogen bonds at the interface are displayed. In (C) and (D) interfacing residues with >20% buried surface area are displayed. (B) Interface formed between the C-lobe of molecule A and the C-lobe of a neighboring molecule B. The positive ΔiG-value reflects the polar nature of this interface that is mainly made up of hydrogen bonds. These connect Ile 4320 and Lys 4270, Glu 4315 and Gln 4272, Asn 4318 and Arg 4327, and Ile 4320 and Arg 4327, of the C-lobes of molecules A and B, respectively. (C) Interface between the C-lobe of molecule A and the N-lobe of another copy of molecule A. This lattice interface is at least partially hydrophobic. Only few residues are buried on each molecule. These include Ile 4276, Gln 4279, and Trp 4280 of the C-lobe and Glu 4177, Cys 4184, and Val 4186 of the neighboring N-lobe, respectively. When considering additional contacts formed between the N-lobe of molecule A and this copy of molecule B (−x,−y + 1,z−1/2) (not shown), the ΔiG-value amounts to 2.6 kcal/mol, demonstrating that this intermolecular interface is rather polar overall. (D) Interface formed between residues in the C-lobe and linker region of molecule A and the N-lobe of a neighboring copy of molecule B. This interface is rather polar and includes a total of five hydrogen bonds that are formed between Leu 4254 and Gly 4011, Leu 4254 and Arg 4013, Ser 4304 and Arg 4013 (two hydrogen bonds), and Gly 4253 and Arg 4013 of the C-lobe and neighboring N-lobe, respectively. When considering additional contacts formed between the N-lobe of molecule A and this copy of molecule B (−y + 1,x−y +1,z) (not shown), the interaction has an even more positive ΔiG-value of 1.5 kcal/mol.