DNA-Directed Protein Biosynthesis

Genetic code The relationship between triplets of nucleotide bases in messenger RNA and the amino acids incorporated into a protein in DNA-directed protein biosynthesis. 

The success of modern biochemistry in explaining such processes as DNA replication, protein biosynthesis, and enzyme catalysis is a direct result of developments in preparatory, instrumental, and computational procedures that have led to the determination of large numbers of structures of biological macromolecules by techniques based on X-ray diffraction. 

Cellular protein biosynthesis involves the following steps. One strand of double-stranded DNA serves as a template strand for the synthesis of a complementary single-stranded messenger ribonucleic acid (mRNA) in a process called transcription. This mRNA in turn serves as a template to direct the synthesis of the protein in a process called translation. The codons of the mRNA are read sequentially by transfer RNA (tRNA) molecules, which bind specifically to the mRNA via triplets of nucleotides that are complementary to the particular codon, called an anticodon. Protein synthesis occurs on a ribosome, a complex consisting of more than 50 different proteins and several stmctural RNA molecules, which moves along the mRNA and mediates the binding of the tRNA molecules and the formation of the nascent peptide chain. The tRNA molecule carries an activated form of the specific amino acid to the ribosome where it is added to the end of the growing peptide chain. There is at least one tRNA for each amino acid. 

Protein polymers based on Lys-25 were prepared by recombinant DNA (rDNA) technology and bacterial protein expression. The main advantage of this approach is the ability to directly produce high molecular weight polypeptides of exact amino acid sequence with high fidelity as required for this investigation. In contrast to conventional polymer synthesis, protein biosynthesis proceeds with near-absolute control of macromolecular architecture, i.e., size, composition, sequence, topology, and stereochemistry. Biosynthetic polyfa-amino acids) can be considered as model uniform polymers and may possess unique structures and, hence, materials properties, as a consequence of their sequence specificity [11]. Protein biosynthesis affords an opportunity to completely specify the primary structure of the polypeptide repeat and analyze the effect of sequence and structural uniformity on the properties of the protein network. 

RNA directs biosynthesis of various peptides and proteins essential for any living organisms. Protein biosynthesis seems to be catalysed by mRNA rather than protein-based enzymes and occur on the ribosome. On the ribosome, the mRNA acts as a template to pass on the genetic information that it has transcribed from the DNA. The specific ribonucleotide sequence in mRNA forms an instruction or codon that determines the order in which different amino acid residues are to be joined. Each instruction or codon along the mRNA chain comprises a sequence of three ribonucleotides that is specific for a given amino acid. For example, the codon U-U-C on mRNA directs incorporation of the amino acid phenylalanine into the growing protein. 

Protein biosynthesis is directed by a special kind of RNA called messenger RNA, or mRNA, and takes place on knobby protuberances within a cell called ribosomes. The specific ribonucleotide sequence in mRNA acts like a long coded sentence to specify the order in which different amino acid residues are to be joined. Each of the estimated 100,000 proteins in the human body is synthesized from a different mRNA that has been transcribed from a specific gene segment on DNA. 

The direction of protein biosynthesis is from the amino terminus to the carboxyl terminus, the mRNA being translated in the 5 — 3 direction as in DNA synthe-... 

Base-pair hydrogen bonding of the Watson-Crick type is fundamental in all biological processes where nucleic acids are involved. These processes, which are chiefly DNA replication and protein biosynthesis [650, 651], were understood only at the molecular level when Watson and Crick discovered the three-dimensional structure of DNA [27, 527J. This structure consists of two polynucleotide chains running in opposite directions (antiparallel), and twisted into a right-handed double helix. The hydrophobic purine and pyrimidine bases are stacked in the center... 

The primary cellular function of RNA is to direct biosynthesis of the thousands of diverse peptides and proteins required by an organism—at least 100,000 in a human. The mechanics of protein biosynthesis appear to be catalyzed by mRNA rather than by protein-based enzymes and lake place on ribosomes, small granular particles in the cytoplasm of a cell that consist of about 60% ribosomal RNA and 40% protein. On the ribosome, mRNA serves as a template to pass on the genetic information it has transcribed from DNA. 

Protein biosynthesis is directed by DNA through the agency of several types of ribonucleic acid called messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). There are two main stages in protein biosynthesis transcription and translation. 

As shown in Figure 6-16, the activated amino acid is attached to the end of its specific /RNA molecule. The function of this aminoacyl /RNA molecule is to place the amino acid that it is carrying in the proper sequence position on the template. Triplets of nucleotides— called anticodons—in the /RNA molecule (Fig. 6-16) are attracted to the complementary codon of mRNA). The amino acid carried by its specific /RNA is thus brought to the correct position on the mRNA codon. Since the anticodon on the /RNA is identical to the codon on DNA (except thymine replaces uracil), the DNA directs the amino acids in the protein-forming chain. The process of protein biosynthesis can now be considered. 

Two forms of initiation factor 2 (mol. wt. 9.0 x 10 ) have been isolated from E. coli extracts and tested for their ability to support j8-o-galactosidase biosynthesis in a phage DNA-directed in vitro protein biosynthesis system. Only the IF-2a form was found to function in jS-o-galactosidase biosynthesis. 

Alkaloids have evolved in plants as powerful defence compounds against herbivores. Although many of them interfere with neuroreceptors and neuronal signal transduction, several others have cytotoxic properties, directed against animal and microbial cells. The present review has tried to summarize some of the molecular targets that are involved in this process. Alkaloids that interfere with microtubules, with DNA (intercalation, topoisomerase inhibition), with protein biosynthesis, and with membrane stability, apparently induce apoptosis, thus leading to cell death. It is very likely however, that many more targets exist that have not been detected, or are not yet correctly understood in this context. 

The nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are the chemical carriers of a cell s genetic information. Coded in a cell s DNA is the information that determines the nature of the cell, controls the cell s growth and division, and directs biosynthesis of the enzymes and other proteins required for cellular functions. 

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