Cysteine, structure

Covalent bonds, 15,18-19,109 Covalent states, 47, 53, 145 Cysteine, structure of, 110... 

Penicillamine (PSH), the dimethyl derivative of cysteine (structure given in Fig. 4), is not a natural metabolite but its reaction with chromate at pH 7 has been investigated because of its possible role as a detoxifying agent in chromate poisoning. In 1970 Sugiura, Hojo... 

The primary structure of a peptide is given by its ammo acid sequence plus any disulfide bonds between two cysteine residues The primary structure is determined by a systematic approach m which the protein is cleaved to smaller fragments even individual ammo acids The smaller fragments are sequenced and the mam sequence deduced by finding regions of overlap among the smaller peptides... 

Tertiary structure also refers to the overall shape of a molecule, especially to structures stabilized by disulfide bridges (cystine) formed by the oxidation of cysteine mercapto groups. 

Fig. 1. Model of a ligand gated ion channel (LGIC) where (a) is the structure of a generic LGIC subunit showing the two cysteine (Cys) residues common to all LGIC subunits, and (b) shows the arrangement of five such subunits as a pentamer having psuedo-cyclic symmetry delineating a gated, fluid-filled...

A second example is that of an Ala-to-Cys mutation, which causes the fonnation of a rare SH S hydrogen bond between the cysteine and a redox site sulfur and a 50 mV decrease in redox potential (and vice versa) in the bacterial ferredoxins [73]. Here, the side chain contribution of the cysteine is significant however, a backbone shift can also contribute depending on whether the nearby residues allow it to happen. Site-specific mutants have confirmed the redox potential shift [76,77] and the side chain conformation of cysteine but not the backbone shift in the case with crystal structures of both the native and mutant species [78] the latter can be attributed to the specific sequence of the ferre-doxin studied [73]. 

Two cysteine residues in different parts of the polypeptide chain but adjacent in the three-dimensional structure of a protein can be oxidized to form a disulfide bridge (Figure 1.4). The disulfide is usually the end product of air oxidation according to the following reaction scheme ... 

CH2SH + 1/2 O2 -CH2-S-S-CH2 + H2O Disulfide bonds form between the side chains of two cysfeine residues. Two SH groups from cysteine residues, which may be in different parts of the amino acid sequence but adjacent in the three-dimensional structure, are oxidized to form one S-S (disulfide) group. 

The side chains of the 20 different amino acids listed in Panel 1.1 (pp. 6-7) have very different chemical properties and are utilized for a wide variety of biological functions. However, their chemical versatility is not unlimited, and for some functions metal atoms are more suitable and more efficient. Electron-transfer reactions are an important example. Fortunately the side chains of histidine, cysteine, aspartic acid, and glutamic acid are excellent metal ligands, and a fairly large number of proteins have recruited metal atoms as intrinsic parts of their structures among the frequently used metals are iron, zinc, magnesium, and calcium. Several metallo proteins are discussed in detail in later chapters and it suffices here to mention briefly a few examples of iron and zinc proteins. 

The 12 residues between the second cysteine zinc ligand and the first histidine ligand of the classic zinc finger motif form the "finger region". Structurally, this region comprises the second p strand, the N-terminal half of the helix and the two residues that form the turn between the p strand and the helix. This is the region of the polypeptide chain that forms the main interaction area with DNA and these interactions are both sequence specific. 

The world of zinc-containing DNA-binding proteins is by no means exhausted by these three subfamilies. Several other subfamilies are already known with different three-dimensional structures and different sequence patterns of cysteine and histidine residues that form the zinc ligands. Further subfamilies may well be discovered as the genomes of different species are sequenced whether or not any fundamentally new principles for DNA-protein recognition will be discovered amongst these new subfamilies remains to be seen. 

Lysozyme from bacteriophage T4 is a 164 amino acid polypeptide chain that folds into two domains (Figure 17.3) There are no disulfide bridges the two cysteine residues in the amino acid sequence, Cys 54 and Cys 97, are far apart in the folded structure. The stability of both the wild-type and mutant proteins is expressed as the melting temperature, Tm, which is the temperature at which 50% of the enzyme is inactivated during reversible beat denat-uration. For the wild-type T4 lysozyme the Tm is 41.9 °C. 

The classic zinc fingers, the DNA-binding properties of which are discussed in Chapter 10, are small compact domains of about 30 residues that fold into an antiparallel p hairpin followed by an a helix. All known classic zinc fingers have a zinc atom bound to two cysteines in the hairpin and two histidines in the helix, creating a sequence motif common to all zinc finger genes. In the absence of zinc the structure is unfolded. 

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