The editing enzyme double-stranded RNA adenosine deaminase includes a DNA binding domain, Z alpha, which is specific for Left-handed Z-DNA, The 2.1 angstrom crystal structure of Z alpha complexed to DNA reveals that the substrate is in the left-handed Z conformation. The contacts between Z alpha and Z-DNA are made primarily with the "zigzag" sugar-phosphate backbone, which provides a basis for the specificity for the Z conformation. A single base contact is observed to guanine in the syn conformation, characteristic of Z-DNA. Intriguingly, the helix-turn-helix motif, frequently used to recognize B-DNA, is used by Z alpha to contact Z-DNA.