An approach to calculating molecular electronic structures of active-site clusters in the presence of protein environments has been developed. The active-site cluster is treated by density functional theory. The protein field, together with the reaction field arising mainly from solvent, is obtained from a finite-difference solution to the Poisson-Boltzmann equation with three dielectric regions, and then these are coupled to the density functional calculation by a self-consistent iterative procedure. The method is applied to compute redox potentials of ferredoxin from Anabaena 7120 and phthalate dioxygenase reductase (PDR) from Pseudomonas cepacia, both having similar [Fe2S2(SR)4] active-site clusters. The calculated redox potentials, -1.007 V and -0.812 V in 0.05 M ionic strength for ferredoxin and PDR, respectively, deviate significantly from experimental values of -0.440 and -0.174 V. However, the calculated data reproduce the experimental trend fairly well. The calculated redox potential for PDR is 195 mV more positive than that for ferredoxin, comparing very well with the experimental value of 266 mV. The energy decomposition scheme reveals that the protein field plays a key role in differentiating the redox potentials of these two proteins.