X‐ray structural analysis of compensating mutations at the barnase‐barstar interface

The crystal structure of the barstar mutants (Y29P) and (Y29D, Y30W) as well as that of the complexes of barstar(Y29P) with wild-type barnase and barnase(H102K) have been determined. These barstar mutants compensate for the dramatic loss of barnase-barstar interaction energy caused by a single mutation of the barnase active site His-102 to a lysine. The latter introduces an uncompensated charge in the pocket at the surface of barstar where Lys-102 is located. The analysis of the structures suggests a mechanism for this compensation based on the solvation of the charge of Lys-102. Additional compensation occurs through the formation of a hydrogen bond.