In the perspective of a sustainable energy economy, CO2 reduction is attracting increasing attention as a key Step toward the synthesis of fuels and valuable chemicals. A possible strategy to develop novel conversion catalysts consists in mimicking reaction centers available in nature, such as those in enzymes in which Fe, Ni, and Cu play a-major role as active metals. In this respect, NiCu shows peculiar activity for both water-gas shift and methanol synthesis reactions. The identification of useful descriptors to engineer and tune the reactivity of a surface in the desired way is one Of the main objectives of the c science of catalysis, with evident applicative interest, as in this case. To this purpose, a crucial issue is the determination of the relevant active sites and rate-limiting steps. We show here that this approach can be exploited to design and tailor the catalytic activity and selectivity of a NiCu surface.