[2Fe-2S] ferredoxins act as electron carriers in photosynthesis by mediating the transfer of electrons from photosystem I to various enzymes such as ferredoxin:NADP(+):reductase (FNR). We have analyzed by density functional theory the possible variations of the electronic properties of the [2Fe-2S] ferredoxin, from the cyanobacterium Anabaena, depending on the redox-linked structural changes observed by X-ray diffraction at atomic resolution (Morales, R.; et al. Biochemistry 1999, 38, 15764-15773). The present results point out a specific and concerted role of Ser47, Phe65, and Glu94 located at the molecule surface, close to the iron-sulfur cluster. These residues were already known to be crucial for efficient electron transfer to FNR (e.g., Hurley, J. K.; et al. Biochemistry 1997, 36, 11100-11117). Our calculations suggest that the Glu94 carboxylate negative charge regulates the electron charge delocalization between the Ser47 CO group and the Phe65 aromatic ring, depending on the redox state. The Glu94 carboxylate is stabilized by a strong hydrogen bond implicating a hydroxyl-containing side chain (i.e., Ser or Thr) at location 47. We propose that the Phe65 ring acts as an intermediary carrier receiving the reducing electron prior to its transfer from the reduced Fd to FNR, in view of its central role in the Fd-FNR interaction.