Protein synthesis enzyme catalysis

The field of synthetic enzyme models encompasses attempts to prepare enzymelike functional macromolecules by chemical synthesis [30]. One particularly relevant approach to such enzyme mimics concerns dendrimers, which are treelike synthetic macromolecules with a globular shape similar to a folded protein, and useful in a range of applications including catalysis [31]. Peptide dendrimers, which, like proteins, are composed of amino acids, are particularly well suited as mimics for proteins and enzymes [32]. These dendrimers can be prepared using combinatorial chemistry methods on solid support [33], similar to those used in the context of catalyst and ligand discovery programs in chemistry [34]. Peptide dendrimers used multivalency effects at the dendrimer surface to trigger cooperativity between amino acids, as has been observed in various esterase enzyme models [35]. 

Molecular complexation is a precondition for receptor functions such as substrate selection, substrate transportation, isomeric differentiation, and stereoselective catalysis. Although the investigation of such functions with synthetically derived compounds is a relatively new development in chemistry, they are well known and extensively studied functions in the biological domain. Evolution, gene expression, cell division, DNA replication, protein synthesis, immunological response, hormonal control, ion transportation, and enzymic catalysis are only some of the many examples where molecular complexation is a prerequisite for observing a biological process. 

The x-ray crystallographic analysis of protein structures is a remarkably successful technique. Since the publication of the first protein structure, that of myoglobin in 1958, many other protein structures have been determined. The resulting structural details often approaching atomic level have led to great insights into enzyme catalysis, hormone function, the organisation of the immune system, the molecular architecture of virus particles and protein synthesis. Why then should such an apparently successful technique need synchrotron radiation ... 

ID 1MME3. Ribozymes, or RNA enzymes, catalyze a variety of reactions, primarily in RNA metabolism and protein synthesis The complex three-dimensional structures of these RNAs reflect the complexity inherent in catalysis, as described for protein enzymes in Chapter 6. (c) A segment of mRNA known as an intron, from the ciliated protozoan Tetrahymena thermophila (derived from PDB ID 1GRZ). This intron (a ribozyme) catalyzes its own excision from between exons in an mRNA strand (discussed in Chapter 26). 

Metal ions are clearly essential for the ribonucleoside triphosphate reductase isolated from the filamentous cyanophyte, Anabaena 7119, one of the many blue-green algae that depend on deoxyadenosylcobalamin for deoxyribonucleotide synthesis The purified enzyme possesses a molecular weight of 72,000 (estimated by gel filtration) with no subunit structure. It does not reduce ribonucleotides in the absence of divalent cations Ca" " is most effective but Mg" " and Mn" also support enzyme catalysis. Judging from their optimum concentration (5-10 mM) the metal ions are not only necessary to complex the substrate triphosphate but should have an effect on the enzyme protein itself. 

The large (SOS) ribosomal subunit is where protein synthesis, catalyzed formation of peptide bonds, takes place. In light of the discoveries by Thomas Cech and Sidney Altman of ribozymes, RNA molecules that behave as enzymes, the question of catalysis of protein synthesis by RNA or proteins in the ribosome was a major one. The 3 OS ribosomal subunit is where transfer RNAs bind with ribosomal RNA codons. The 50S ribosomal subunit can be further separated into a 23S secondary subunit and a smaller 5S secondary subunit that are normally held together by protein molecules. The 23S subunit includes 3045 nucleotides and 31 proteins. There are six discrete RNA domains in the S23 unit particle. The 5S unit effectively adds a seventh domain. The proteins permeate the exterior of the RNA of S23, but are located over 18 A distant from the active site of catalytic protein bond formation. The structures of complexes of the S23 subunit with two inactive substrate molecules suggest mechanistic similarities to the enzyme chymotrypsin. The S23 structure indicates that an adenine base at the active site plays a role analogous to that of histidine-... 

Biochemistry continues to have a major influence on the development of peptide synthesis. Peptide bond formation via catalysis with proteolytic enzymes has the promise of products with absolute chiral purity and should also be free from many side reactions encountered in synthesis by the methods of organic chemistry. Therefore coupling with the help of enzymes (cf page 57) is receiving growing attention. Perhaps even more exciting is the exploitation of ribosomal protein synthesis for the production of selected target peptides, such as insulin. In recent years preparation of the necessary DNAs became almost routine and hence this avenue of peptide synthesis broadened to a major area that transcends the boundaries of this book. 

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