The antigenic structure of bovine serum albumin. Evidence for multiple, different, domain-specific antigenic determinants.

Using antiserum to native bovine albumin and antigenically active fragments of the protein, we have isolated antibodies directed to each of the three domains and to several subdomains of the albumin molecule. Using albumin and these fragments as inhibitors of the reaction between 125I-albumin and any given antibody population, we have demonstrated that: (a) each domain of albumin is antigenically distinct from each of the other domains; (b) each domain possesses a minimum of two different antigenic determinants; and (c) the entire albumin molecule possesses a minimum of six different, nonrepeating, antigenic determinants.     

High affinity binding of thrombin to platelets. Inhibition by tetranitromethane and heparin

[¹²⁵I] iodo-α-thrombin has been modified at the macromolecular substrate binding site in order to study the importance of this region in the platelet-thrombin interaction. Modification was effected by the nitration of tyrosine residues with tetranitromethane. This chemical modification abolished the ability of the enzyme to bind with a high affinity to the platelet surface but did not significantly alter low affinity binding. The presence of heparin was also found to inhibit high affinity binding. These results indicate that the high affinity binding site interacts with the fibrinogen binding region of the thrombin molecule and suggests that there are two distinct classes of binding sites for thrombin on the platelet membrane.     

Visualization of drug-nucleic acid interactions at atomic resolution. III. Unifying structural concepts in understanding drug-DNA interactions and their broader implications in understanding protein-DNA interactions.

Structural information afforded by the X-ray crystallographic studies of ethidium-dinucleoside monophosphate crystalline complexes described in the preceding two papers has led to a detailed model for ethidium-DNA binding. Features of ethidium-DNA binding, in turn, have led to unifying structural concepts in understanding a wide range of drug-DNA interactions. It is possible that these concepts have still broader implications in understanding the nature of protein-DNA interactions.This paper begins by summarizing the stereochemical aspects of ethidium-DNA, actinomycin-DNA and irehdiamine-DNA binding, molecules that use intercalative and kinked-type geometries in binding to DNA. It then describes superhelical DNA structures formed by kinking DNA periodically varying numbers of base-pairs apart. κ-kinked B DNA, a structure formed by kinking DNA every ten base-pairs, is a left-handed superhelical structure that may be utilized in the organization of DNA within the nucleosome in chromatin. β-kinked B DNA is a right-handed superhelical structure formed by kinking DNA every two base-pairs. It is possible that premelting conformational changes occur in DNA which utilize elements of this structure. This would expose base-pairs to solvent denaturation, and could lower the activation energy necessary for strand separation during DNA denaturation. RNA polymerase and other DNA melting proteins could capitalize on this type of premelting conformational change when binding to DNA.The concept that conformational flexibility exists in DNA structure (and that drug intercalation is a phenomenon that reflects this flexibility) can, in addition, explain a wide variety of physicochemical data about DNA. In this paper we discuss the nature of these data in detail.