The blue-copper proteins azurin from Pseudomonas aeruginosa, azurin from Alcaligenes denitrificans, andthe mutant Met121Gln of azurin from Alcaligenes denitrificans have been investigated by resonance Ramanspectroscopy. Large deuterium isotope shifts up to 6 cm-1 have been observed for bands in the 350−460cm-1 range after incubation of the apoproteins in D2O and subsequent reconstitution with copper. The shiftsderive from the deuteration of the amide hydrogens of Asn47 and Phe114 that form a hydrogen bond withthe sulfur of the copper-coordinated cysteine. This observation reveals the coupling of the copper−sulfur andsulfur−hydrogen vibrations and indicates that these amide groups have to be taken into account to properlydescribe the electronic structure of the blue-copper site.