Structure disulphide linkages

X-ray diffraction analysis shows the protein to be a globular structure, consisting of four a-helical stretches interrupted by bends and loops. It appears devoid of any //-conformation and contains a single stabilizing disulphide linkage involving cysteine numbers 58 and 105 (Figure 5.1). 

The biological activities of several other interleukins also render them likely candidates for therapeutic application. IL-5 represents one such candidate. IL-5 is a 115 amino acid glycoprotein produced mainly by activated T lymphocytes and also by mast cells. It functions as a homodimer, exhibiting a molecular mass of 45 kDa. The individual polypeptide chains interact non-covalently and the overall dimeric structure is stabilized by two interchain disulphide linkages between cysteines 42 and 84 of each chain. Removal or alterations of the cytokine s carbohydrate side-chain does not appear to affect its biological activity. 

Mature insulin consists of two polypeptide chains connected by two interchain disulphide linkages. The A-chain contains 21 amino acids, whereas the larger B-chain is composed of 30 residues. Insulins from various species conforms to this basic structure, while varying slightly in their amino acid sequence. Porcine insulin (5777 Da) varies from the human form (5807 Da) by a single amino acid, whereas bovine insulin (5733 Da) differs by three residues. 

The most common thiol role is participation in the overall structural integrity of proteins. Except for the special case of the disulphide linkage this can be viewed as a rather nonspecific and passive function. This is not to imply that in any given circumstance that another amino acid side chain might serve as effectively as cysteine or methionine, but rather to point out that these amino acids are no more critical in their place than are any other in theirs. From an experimental standpoint there is one... 

The role of tryptophan-62 in reactions catalysed by lysozyme has been investigated. Studies on the regeneration of a reduced form of hen egg-white lysozyme by glutathione have yielded information on the folding mechanism of the reduced enzyme. The structure of the reactive site surrounding the two central disulphide linkages of lysozyme has been investigated. ... 

The luminescence of bovine a-lactalbumin at 77 °K has been compared with that of lysozyme. a-Lactalbumin has a fluorescence spectrum that shows vibrational fine structure, an abnormal phosphorescence spectrum, a high fluorescence phosphorescence ratio, and an abnormal phosphorescence decay these properties are due largely to the proximity of tryptophanyl residues to the disulphide linkages. 

Yeasts are single-cell fungi with cell walls consisting of two interlocking structures, either of which is sufficient to keep the characteristic shape. One structure is made entirely of glucan (a poly-anhydride of glucose), and the other is a mannan-protein complex bound to disulphide linkages (Nickerson, Falcone and Kessler, 1961). Only when both structures are broken is the cytoplasm extruded (Bacon et al.y 1965). 

The introduction of redox-sensitive linkages, such as the disulphide group, has been used to prepare liposomes that are susceptible to the lower intracellular redox potential relative to the extracellular environment. Symmetrical disulphides are synthesised by oxidation of thiol-containing structures [64, 130, 131] (see Fig. 7),... 

Figure 4 Structural features and diversity of bacteriocins. Solution NMR structures are shown for (a) the lantibiotic actagardine (PDB code 1AJ1) the pedocin-like bacteriocins (b) curvacin A (PDB code 2A2B) and (c) leucocin A (PDB code 1CW6) (d) the A and B chain of the two-chain bacteriocin lactococcin G in DPC micelles (PDB codes 2JPJ and 2JPK) and the cyclic bacteriocins (e) subtilosin (PDB code 1AJ1) and (f) AS-48 (PDB code 1E68). Disulphide bonds and lanthionine linkages are shown in ball-and-stick. Chain termini are labelled N and C and the cyclisation points on the cyclic peptides are labelled with residue numbers.

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