Single mutations outside the active site affect the substrate specificity in a β-glycosidase

► We selected single mutations altering the substrate specificity of a β-glycosidase ► These mutations are far from the active site and concentrated in the C-terminal half ► These mutations are inserted in contact networks that connect to the active site ► Mutations on the same network have similar effects on the specificity and structure ► We propose that mutation effects may reach the active site via contact networks