Disulphide bridges, structure

A small number of proteins, and again insulin is an example, are synthesized as pro-proteins with an additional amino acid sequence which dictates the final three-dimensional structure. In the case of proinsulin, proteolytic attack cleaves out a stretch of 35 amino acids in the middle of the molecule to generate insulin. The peptide that is removed is known as the C chain. The other chains, A and B, remain crosslinked and thus locked in a stable tertiary stiucture by the disulphide bridges formed when the molecule originally folded as proinsulin. Bacteria have no mechanism for specifically cutting out the folding sequences from pro-hormones and the way of solving this problem is described in a later section. 

Figure 2. Correspondence of the calculated backbone trace with that of the reported backbone for BP2 [19], As well, the calculated disulphide bridges are included to illustrate the important role they play in protein structure, binding certain regions together. 

It is secreted by acidophil cells. Human growth hormone has a single straight chain polypeptide structure containing two intramolecular disulphide bridges and is composed of 188 amino acids. 

Unlike polysaccharides, proteins do not have branched chains, but several chains may be linked together via disulphide bridges rather than peptide bonds. The primary structure of ox insulin is shown in Fig. S.A2. The protein consists of two peptide chains which are linked via the formation of the disulphide bridges. Disulphide bridges are formed by the condensation of the thiol groups of two cysteine residues. 

Growth hormone (somatotropin GH) is a protein hormone produced in specific cells (somatotrophs) of the pituitary gland. It comprises a single polypeptide chain of about 190 amino acids which folds, with formation of two disulphide bridges, to a compact tertiary structure (see also Addendum, p. 289). Amino acid sequences have been determined for GHs from several species [1,2] and these reveal a considerable amount of species variation in particular, human GH shows extensive differences from the GHs of non-primate mammals, and this has been interpreted as indicating a rapid rate of evolution for the GH gene in the primates [3,4], Differences in biological properties between human and non-primate GHs have also been observed, and will be considered later. 

Pituitary prolactin is a protein hormone comprising a single polypeptide chain of about 200 amino acid residues and 3 intrachain disulphide bridges [1,2]. It is structurally homologous with growth hormone (GH) as is discussed in Chapter 13 (Fig. 1). Amino acid sequences of prolactins from various different species have been described [1-3] they show a considerable amount of species variation, which is most notable in the case of the prolactins of the rat and mouse, which differ from prolactins of other mammals at about 40% of all amino acid residues [3,4]. 

There are distinct receptors for both IGF-I and IGF-II. The IGF-I receptor is similar in structure to that for the insulin receptor, having a disulphide bridge-linked subunit (a-j8)2 structure [49-52]. The a subunit has a molecular mass of 130 kDa which is capable of binding IGF-I. The 95 kDa j8 subunit of the IGF-I receptor, like that for the insulin receptor, exhibits a tyrosyl kinase activity. In marked contrast, however, the IGF-II receptor is a monomeric protein of molecular mass 220 kDa [53,54] with no known intrinsic activity. 

Blake, C. C. F., Ghosh, M., Harlos, K., Avezoux, A., and Anthony, C., 1994, The active site of methanol dehydrogenase contains a disulphide bridge between adjacent cysteine residues. Nature, Structural Biology 1 1029105. 

As previously stated, these cyclic peptides have shown significant bioactivity in different screening regimes and a strong structure-activity relationship has been noted by several workers, with the disulphide bridge in the ulithiacyclamides e.g. 17,18) making these the most cytotoxic of the compounds isolated from L. Patella. It is thought that the... 

Da) characteristic secondary structure, with a specific content of or-helix, j3-sheet and disordered peptide chain conformations isoelectric point 5.4-5.5 presence of two disulphide bridges and a free thiol group... 

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