This paper presents a strategy to tune the orientation of immobilized proteins on electrodes of general applicability to different types of proteins. We orient ferredoxin:NADP(+) reductase molecules onto a modified gold electrode by introducing a genetically engineered metal binding site on a selected region of the protein surface and covering the gold surface with a self-assembled monolayer of thiols appended with nitrilotriacetic acid groups complexed with metal transition ions. Two mutants were designed to have a histidine pair (His-X-3-His) on surface-exposed alpha -helices located in one of the two protein domains. It was first demonstrated that the mutant proteins in solution retain their full activity and that the kinetic constants of the redox catalytic steps are not affected by the mutations. The enzyme-modified gold electrodes were then analyzed for the amount and distribution of protein on their surface and for their activity using atomic force microscopy and cyclic voltammetry. The two electrode-bound mutant enzymes manifested differences in the amount and distribution of bound molecules, in the kinetic constants of their redox catalytic steps, and most interestingly, in their ability to transfer electrons to a redox mediator covalently attached to the self-assembled monolayer. We conclude that the position of the mutated alpha -helix determined the orientation of the protein with respect to the surface and. as a result, its competence to establish direct electrical communication with the electrode.