Additional information
by Henry M. Sobell (Author)
The author is internationally renowned for his pioneering contributions to the understanding of how the anticancer agent, actinomycin D, binds to DNA and exerts its mechanism of action. Using the technique of X-ray crystallography, he and his research colleague, Shri C. Jain, solved the structure of a crystalline complex containing actinomycin and deoxyguanosine in the early 1970's, and this information led them to propose a model that is now widely accepted to understand the general
features of how actinomycin binds to DNA.According to this model, the phenoxazone ring system on actinomycin intercalates between adjacent base pairs, while pentapeptide chains lie in the narrow groove of the B- helix, forming hydrogen bonds (in the case of d (pGpC) sequences) with guanine residues on opposite chains. Although X-ray crystallographic studies of actinomycin complexed to a number of different self-complementary oligonucleotides have now confirmed the overall features of this model, the precise nature of the DNA conformation remains unknown due to problems inherent in refining large structures with limited resolution data. Implicit in the original model was the assumption that actinomycin binds to B-DNA or to a distorted form of B-DNA. The possibility that actinomycin might bind to some other discretely different DNA conformational state was not envisioned at that time.
