Structural transformation of the canonical right-handed helix, B-DNA, to the non-canonical left-handed helix, Z-DNA, can be induced by the Z alpha domain of the human RNA editing enzyme ADAR1 (hZ alpha(ADAR1)). To characterize the site-specific preferences of binding and structural changes in DNA containing the 2'-O-methyl guanosine derivative ((m)G), titration of the imino proton spectra and chemical shift perturbations were performed on hZ alpha(ADAR1) upon binding to Z-DNA. The structural transition between B-Z conformation as the changing ratio between DNA and protein showed a binding affinity of the modified DNA onto the Z-DNA binding protein similar to wild-type DNA or RNA. The chemical shift perturbation results showed that the overall structure and environment of the modified DNA revealed DNA-like properties rather than RNA-like characteristics. Moreover, we found evidence for two distinct regimes, "Z-DNA Sensing" and "Modification Sensing", based on the site-specific chemical shift perturbation between the DNA (or RNA) binding complex and the modified DNA-hZ alpha(ADAR1 )complex. Thus, we propose that modification of the sugar backbone of DNA with 2'-O-methyl guanosine promotes the changes in the surrounding alpha 3 helical structural segment as well as the non-perturbed feature of the beta-hairpin region. (C) 2020 Elsevier Inc. All rights reserved.