Proteins amino acid incorporation

The structures of amino acids incorporated into polypeptides and proteins may be characterized by a pair of dihedral angles involving the so-called a carbon for each amino acid. 

A nonsense codon may appear that would then result in the premature termination of amino acid incorporation into a peptide chain and the production of only a fragment of the intended protein molecule. The probabihty is high that a premamrely terminated protein molecule or peptide fragment will not function in its assigned role. 

T. Kohno, D. Kohda, M. Haruki, S. Yokoyama, and T. Miyazawa, Non-protein amino acid furanomycin, unlike isoleucine in chemical structure, is changed to isoleucine tRNA by isoleucyl-tRNA synthetase and incorporated into protein. J. Biol. 

Ritchie GP, Ho IK. 1982. Effects of chlordecone and mirex on amino acids incorporation into brain and liver proteins in the mouse. Neurotoxicology 3(4) 243-247. 

Ribosomal synthesis of peptides proceeds through translation of messenger ribonucleic acid (mRNA) and utilizes the 20 primary L-a-amino acids. These amino acids are incorporated with the use of specific transfer ribonucleic acid (tRNA) codons. The 20 primary a-amino acids, with the exception of glycine that is achiral, are characterized by an L-configuration at the a-position (Figure 1). In general, most proteins are found to be composed of these 20 L-a-amino acids, as such they are referred to as protein amino acids. 

Structure and Function of Peptidyl Carrier Protein Domains Structure and Function of Adenylation Domains Structure and Function of Condensation Domains Structure and Function of Thioesterase Domains Multidomain NRPS Structural Information PCP-C didomain structure PCP-TE didomain structure Structure of a C-A-PCP-TE termination module Pathways to Nonproteinogenic Amino Acids Incorporated into NRP Natural Nonproteinogenic Amino Acids Present as Cellular Metabolites Modification of Proteinogenic Amino Acids Nonproteinogenic Amino Acids Derived from Multistep Pathways Tailoring Enzymology in NRP Natural Products Chemical Approaches Toward Mechanistic Probes and Inhibitors of NRPS... 

About 300 different non-protein amino acids occur in plants. They may be incorporated into proteins in place of the correct amino acids. If they are incorporated into enzymes, they can prevent them from functioning. This often leads to death of the animal. For example, azetidine 2-carhoxylic acid in lily-of-the-valley, Comallaria majalis, and several legumes interferes with synthesis or utilization of structurally similar proline (Fig. 11.9). 

Short-term ozone exposures (45 5 pphm, 15 min) of seedlings were followed after 24 hr by non-linear reductions in chlorophyll/g fresh weight and stimulations in fresh weight/organ. The utilization of l C-protein hydrolysate by tissue discs is not only predominantly energy-dependent, but also strictly dependent with respect to inhibition or stimulation upon the time after ozonation. Uptake of labelled amino acids into the soluble pools of tissue discs is sensitive to as little as 15 min of in vivo exposure (45 5 pphm), and incorporation into insoluble protein is sensitive during 15 to 30 min, after which no further reduction is observed for up to 90 min of exposure. The reduction of amino acid influx into the soluble pools is not accountable to a reduction in amino acid tRNA charging, and is probably not due to a reduction in amino acid incorporation. 

Proteins are costly to the cell, requiring hydrolysis of five high-energy phosphate bonds per amino acid incorporated. 

Anabolic activities of testosterone, such as increases in amino acid incorporation into protein and in RNA polymerase activity, have been demonstrated in skeletal muscle. Apart from the direct anabolic effects in specific tissue, androgens antagonize the protein catabolic action of glucocorticoids. The androgen compounds with the greatest ratio of protein anabolic effects to virilizing effects are the 19-nortestosterone derivatives. Compounds that are used clinically (Table 63.3) include nandrolone phenpropionate (Durabolin), nandrolone decanoate... 

While readthrough is usually a detrimental process, in some cases it can help to suppress problems, e.g. arising from premature stop codons present on the DNA level. This type of readthrough, also termed nonsense suppression, leads to the generation of a fraction of the full length protein in addition to the shortened version. Omnipotent suppressors cause nonsense suppression of all three termination codons. In this process, a near cognate tRNA successfully competes with the termination factors such that amino acid incorporation rather than premature termination of translation occurs. Omnipotent suppression can be caused by mutations in various factors involved in the process of translation termination. Nonsense suppression can also result from an aa-tRNA that decodes a termination codon (suppressor tRNA) in this case only one of the termination codons is efficiently suppressed (Hawthorne and Leupold 1974 Stansfield and Tuite 1994). 

Enhancement of amino acid incorporation into proteins... 

L-Canavanine and L-canaline are non-protein amino acids of certain leguminous plants, that function as protective allelochemicals. L-Canavanine is incorporated into de novo synthesized proteins in place of arginTne there is suggestive evidence that formation of such anomalous proteins figures significantly in canavanine s adverse biological effects. Canavanine, however, does not appear to inhibit overall protein synthesis. Thus, an important basis for canavanine s antimetabolic properties resides in the sustained production of biologically aberrant proteins. 

The overall error rate of protein synthesis ( 1 mistake per 104 amino acids incorporated) is not nearly as... 

The polymerization and stabilization of ribosomes are influenced by the presence of potassium and other monovalent cations in the medium, and also by Mg2+. Potassium is thus essential for protein synthesis in that it controls the structural integrity of the ribosomes, but it also appears to facilitate amino acid incorporation by transfer from the RNA to the polypeptide chain in the ribosome. 

There are also changes in the rates of metabolism as red blood cells appear and aerobic processes intensify (Lasker and Theilacker, 1962 Laurence, 1975 Timeyko and Novikov, 1991) during the early phases of ontogenesis. Oxygen consumption increases, as do the number of mitochondria and their protein contents (Abramova and Vasilyeva, 1973 Ozemyuk, 1993). The adenyl nucleotide pool (ATP and ADP) decreases (Milman and Yurovitsky, 1973 Boulekbache, 1981), while the activity of cytochrome oxidase increases (Ozemyuk, 1993). The increased energy metabolism corresponds to a considerable extent with motor activity (Reznichenko, 1980). In the yolk sac, the activity of proteinase, which supplies nitrogenous materials to the embryo, increases, as does the rate of amino acid incorporation into the body proteins. 

Lamborg, M. R. and Zamecnik, P. C. (1960) Amino acid incorporation into the protein by extracts of E. coli. Biochim. Biophys. Acta 42, 206-211. 

SCHEME 19.7 Amber codon suppression strategy for unnatural azido amino acid incorporation in proteins. 

Armentomycin (75) [72] inhibits the growth of bacteria on a synthetic medium. Biosynthesis of this non-protein amino acid is catalyzed by a peroxidase incorporating chlorinated substituents into the molecule without a simultaneous removal of other functional groups. 

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