Polypeptides in nature

In this chapter, we refer to polypeptides and proteins, and we now give a brief resume of some of the terminology needed. A polypeptide in Nature is formed by the condensation, in varying sequences, of the 20 naturally occurring a-amino acids. Structure 28.1 gives the general formula of an amino ... 

Nucleic acids can play roles farbeyond merely harbouring the coding information for proteins. Single-stranded nucleic acids can fold into intricate structures capable of molecular recognition and even catalysis. Three-dimensional structures are specified by the primary structure, namely the deoxynucleotide (or nucleotide, for RNA) sequence (5 - 3, by analogy to the situation in which the amino-acid residue sequence determines the three-dimensional structures of polypeptides. In nature, transfer RNAs (tRNAs) use their three-dimensional shape for molecular recognition, while some ribosomal RNAs (rRNAs) are able to catalyse crucial steps even within the protein synthetic pathways themselves. 

Amino acids, the building blocks for polypeptides, contain both an amine and carboxyl group in the same molecule. The amino acids used to synthesize polypeptides in nature are the a-amino acids, those in which the amine group is located on the a-carbon. The a-carbon is the first carbon attached to the COOH carbon, the second carbon from the COOH is the /3-carbon, the third carbon from the COOH is the -y-carbon, and so on. 

Polymerization reactions proceed either by the step growth or the chain addition mechanisms. Step-growth polymerizations require monomers with at least two functional groups and are involved in the manufacture of several industrially important polymers such as polyamides, polyesters, and in the formation of biopolymers such as polysaccharides, proteins and polypeptides in nature. 

Most polypeptides in nature are longer than 20 to 30 amino acids, the practical limit on the number of amino acids that can be sequenced by repetitive Edman degradation. The special value of cleavage with cyanogen bromide, trypsin, and chymotrypsin is that, at specific peptide bonds, a long polypeptide chain can be cleaved into smaller polypeptide fragments, and each fragment can then be sequenced separately. 

POLYPEPTIDES IN NATURE OXYGEN TRANSPORT BY THE PROTEINS MYOGLOBIN AND HEMOGLOBIN... 

Most biological catalysts are enzymes, i.e., proteins, which are macromolecules (polypeptides) fonned by biopolymerization of amino acids (with elimination of water) some enzymes are huge, with hundreds of monomer units. The 20 amino acid monomers occurring in nature. 

Disulfides. The introduction of disulfide bonds can have various effects on protein stability. In T4 lyso2yme, for example, the incorporation of some disulfides increases thermal stability others reduce stability (47—49). Stabili2ation is thought to result from reduction of the conformational entropy of the unfolded state, whereas in most cases the cause of destabili2ation is the introduction of dihedral angle stress. In natural proteins, placement of a disulfide bond at most positions within the polypeptide chain would result in unacceptable constraint of the a-carbon chain. 

Some of these compounds could be considered as dietary additives, but various other terms, including pesticides, can also be used. They can have beneficial effects on the environment and this aspect will be discussed later. The ionophore monensin, which is an alicyclic polyether (Figure 1), is a secondary metabolite of Streptomyces and aids the prevention of coccidiosis in poultry. Monensin is used as a growth promoter in cattle and also to decrease methane production, but it is toxic to equine animals. " Its ability to act as an ionophore is dependent on its cyclic chelating effect on metal ions. ° The hormones bovine somatotropin (BST) and porcine somatotropin (PST), both of which are polypeptides, occur naturally in lactating cattle and pigs, respectively, but can also be produced synthetically using recombinant DNA methods and administered to such animals in order to increase milk yields and lean meat production. "... 

Determining the Amino Acid Sequence Nature of Amino Acid Sequences Synthe.sis of Polypeptides in the Laboratory... 

ENZYMATIC ANALYSIS WITH CARBOXYPEPTIDASES. Carboxypeptidases are enzymes that cleave amino acid residues from the C-termini of polypeptides in a successive fashion. Four carboxypeptidases are in general use A, B, C, and Y. Carboxypeptidase A (from bovine pancreas) works well in hydrolyzing the C-terminal peptide bond of all residues except proline, arginine, and lysine. The analogous enzyme from hog pancreas, carboxypeptidase B, is effective only when Arg or Lys are the C-terminal residues. Thus, a mixture of carboxypeptidases A and B liberates any C-terminal amino acid except proline. Carboxypeptidase C from citrus leaves and carboxypeptidase Y from yeast act on any C-terminal residue. Because the nature of the amino acid residue at the end often determines the rate at which it is cleaved and because these enzymes remove residues successively, care must be taken in interpreting results. Carboxypeptidase Y cleavage has been adapted to an automated protocol analogous to that used in Edman sequenators. 

Fibrous protein (Section 26.9) A protein that consists of polypeptide chains arranged side by side in long threads. Such proteins are tough, insoluble in water, and used in nature for structural materials such as hair, hooves, and fingernails. 

In striated muscle, there are two other proteins that are minor in terms of their mass but important in terms of their function. Tropomyosin is a fibrous molecule that consists of two chains, alpha and beta, that attach to F-actin in the groove between its filaments (Figure 49-3). Tropomyosin is present in all muscular and muscle-fike structures. The troponin complex is unique to striated muscle and consists of three polypeptides. Troponin T (TpT) binds to tropomyosin as well as to the other two troponin components. Troponin I (Tpl) inhibits the F-actin-myosin interaction and also binds to the other components of troponin. Troponin C (TpC) is a calcium-binding polypeptide that is structurally and functionally analogous to calmodulin, an important calcium-binding protein widely distributed in nature. Four molecules of calcium ion are bound per molecule of troponin C or calmodulin, and both molecules have a molecular mass of 17 kDa. 

Polyamides are macromolecules with acidamide units —CONH—, where the chemical structure of the other parts of the monomers can be aliphatic and/or aromatic. Similar structures are found in nature, for example, polypeptides. Although in principle a large number of potential polyamide structures can be produced, only a few polyamides are produced in industrial scale. 

At the two extremes, lysine is observed as the amino acid most accessible on the surface of proteins while cysteine is the least exposed amino acid. The inaccessibility of cysteine probably stems from the fact that disulfides are typically buried within the polypeptide structure of proteins, whether they are intrachain or interchain in nature, and proteins rarely contain many reduced cysteine thiols. 

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