Three-dimensional structure, relationship biological activity

Structure-Activity Correlations. This detailed knowledge of the three-dimensional structure of insulin led to the recognition that its biological activity resides in an area of the molecule rather than in specific amino acid residues, just as dimerization and further association of the molecule also depend on an intact spatial structure. The foregoing concept is corroborated by structural modifications of the hormone. The last three amino acids of the B chain can be removed without a loss of activity, but cleavage of the C-terminal of the A chain (Asn ) results in a total loss of activity. Amino acids can be replaced inside the chains only if such substitution does not change the overall geometry of the molecule. The structure-activity relationships of insulin derivatives are inconsistent and not always comparable. 

The isolation of extremely thermophilic archaea over the last decade stimulated interest in the proteins of these remarkable organisms. Up to now a considerable number of different proteins from these organisms has been purified and characterized (Table 1). But an understanding of the structural and environmental factors which enable them to be stable and biologically active at temperatures around 100 C is still sparse. Information about the three-dimensional structure of these proteins will be necessary to understand the structure-function relationship of proteins constructed for the upper temperature limits of life. 

Motoc, R. A. Dammkoehler, and G. R. Marshall, in Mathematical and Computational Concepts in Chemistry. N. Trinajstic, Ed., Ellis Horwood, Chichester 1986, pp. 222-257. Three-Dimensional Structure-Activity Relationships and Biological Receptor Mapping. 

For many toxic compounds, particularly the specialists that bind to very specific cell receptor sites, it would stand to reason that the three-dimensional structure of the toxic compound is responsible for its cellular impact. If the toxic compound is a key, then the receptor molecule is a lock, and for many toxic chemicals, differences in the chemical structure of the molecule (analogous to slight differences in the cutouts on the blade of a key) can lead to alterations in its toxicity. Furthermore, if the toxic mechanism by which a compound elicits a biological eflFect is understood, it stands to reason that molecules that share a similar chemical structure may cause similar effects when organisms are exposed to them. The structure-activity relationship, the correlation between the structure of a chemical compound and its biological activity, is the major corollary that can be derived from Fare s writings. 

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