Proteins template theory

A key problem is the in vivo synthesis of chemicals such as proteins and nucleic acids with rigidly specific structures. Spiegelman (1928) gives a clear review. The template theory, which he favors, has ample opportunity for H bond participation. Enzyme action is also conceived as a template reaction (1584). In this case, somewhat less matching is needed, in comparison with the synthesis of genetic material. The enzyme and substrate need fit over only a fairly small percentage of their surface (50). Hydrogen bonds may help achieve this match and thus influence the specificity of the reaction. 

It seems probable that an inhibitor which combined with the surface of the template, either the nucleic acid or the pre-protein portion, would prevent the synthesis of both protein and nucleic acid. This is the case with bacitracin which from its polypeptide nature might be expected to interfere with protein synthesis. Accordingly in Fig. 33 we can tentatively indicate bacitracin as acting by combining with the nucleic acid template and so blocking further protein or nucleic acid synthesis. There is a possible explanation here of the high concentrations of bacitracin required to effect complete inhibition of protein and nucleic acid synthesis. In the experiments described above, protein synthesis is a measure of the overall synthesis of cellular protein whereas it is an essential of the template theory that each template should be responsible for synthesis of a specific protein. It is reasonable to suppose that growth inhibition would be dependent upon inhibition of the formation of a specific protein rather than of all the cell proteins, and that an inhibitor which combined with a template would have an action on the synthesis of specific proteins... 

A question which any speculation about the template theory must take into account is What is the form of the amino acid residue which enters into combination with the template and gives rise to the protein It could be postulated that amino acids themselves are protein precursors, or that small peptides are formed first and that these combine at the template surface. The former postulate would allow for complete randomization of the amino acid residues. It is relevant in this connection to note that neither the formation of extracellular peptides by Staph, aureus (Table XVI) nor the synthesis of glutathione by cell-free extracts of Esch. colt (Samuels, 1953) is sensitive to chloramphenicol, etc., and so the formation of simple peptides cannot be taken as a model of protein syn-... 

DNA has two broad functions replication and expression. First, DNA must be able to replicate itself so that the information coded into its primary structure is transmitted faithfully to progeny cells. Second, this information must be expressed in some useful way. The method for this expression is through RNA intermediaries, which in turn act as templates for the synthesis of every protein in the body. The relationships of DNA to RNA and to protein are often expressed in a graphic syllogism called the central dogma. The concept was proposed by Crick in 1958 and was revised in 1970 to accommodate the discovery of the RNA-dependent DNA polymerase. Crick s original theory suggested that the flow of information was always from RNA to protein and could not be reversed, yet it allowed for the possibility of DNA synthesis from RNA. 

A theory proposing that the effect of steroids is to stimulate amino acid activation and, as a result, protein synthesis is not without objections. If the primary effect of steroid hormones is to activate amino acids, the rate of synthesis of all proteins should be increased in the target organ. In contrast, steroids stimulate the biosynthesis of highly specific proteins, and therefore it seems more logical to assume that the steroids act at a step of the biosynthetic pathway that determines the specificity of the proteins synthesized. Such a mechanism could involve transcription of messenger RNA on DNA template. The rate of incorporation of labeled nucleotide triphosphate into the rapidly labeled nuclear RNA by the methods described by Weiss is markedly decreased in castrated animals. 

In any theory the idea that the whole phage particle is the template must be discarded because the isotope studies have clearly demonstrated that the virus is broken down and only a portion enters the bacterial cell. This reproductive form, if it is such, contains little or no protein hence both specificity of form and hereditary structure must be largely or wholly associated with the virus nucleic acid. If the proteinaceous membrane of the phage is really excluded from the cell, as all the evidence indicates, we are left with the dilemma that phage protein is reproduced either by virtue of specific units smaller than genes (100a) or by unknown long-distance forces. 

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