Due to chemical exchange, the mobility of histidine (His) side chains of proteins is typically difficult to analyze by NMR spectroscopy. Using an NMR approach that is uninfluenced by chemical exchange, we investigated internal motions of the His imidazole NH groups that directly interact with DNA phosphates in the Egr-1 zinc-finger-DNA complex. In this approach, the transverse and longitudinal cross-correlation rates for N-15 chemical shift anisotropy and N-15-H-1 dipole dipole relaxation interference were analyzed together with N-15 longitudinal relaxation rates and heteronuclear Overhauser effect data at two magnetic field strengths. We found that the zinc-coordinating His side chains directly interacting with DNA phosphates are strongly restricted in mobility. This makes a contrast to the arginine and lysine side chains that retain high mobility despite their interactions with DNA phosphates in the same complex. The entropic effects of side-chain mobility on the molecular association are discussed.