Cysteine between

Fig. S.6. UbcH7/E6AP (1C4Z). The surface of UbcH7 is shown with residues interacting with the E6AP HECTdomain shown in blue and the active-site cysteine shown in yellow. E6AP is colored green with the active-site cysteine between the N- and C-lobe shown in yellow.

TRANSPORT Transport of GSH out of cells appears to serve several functions. Among these are (1) transfer of the sulfur atoms of cysteine between... 

Figure 5.8 (A) A 2D EXSY showed exchange of trypanothione between its bound and free forms (mixing time 500 ms) and (B) edited H NMR spectra showed the exchange of C-labeled cysteine between its bound and free forms in the ternary complex. Adapted with permission from S.-C. Yan et al., J. Biol. Inorg. Chem. 8, 689 (2003) [145]. Copyright (2003) Springer Verlag.

Insulin has 51 ammo acids divided between two chains One of these the A chain has 21 ammo acids the other the B chain has 30 The A and B chains are joined by disul fide bonds between cysteine residues (Cys Cys) Figure 27 10 shows some of the infor matron that defines the ammo acid sequence of the B chain... 

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... 

Disulfide bridge (Section 27 7) An S—S bond between the sulfur atoms of two cysteine residues in a peptide or pro tein... 

Calcitonins from several species have been characteri2ed and synthesi2ed. They are all single-chain 32-residue polypeptides (ca 3600 mol wt), although a disulfide link between the first and seventh cysteine residues results in a cycHc stmcture that is indispensable for activity (Eig. 6). 

The side groups of the amino acids vary markedly in size and chemical nature and play an important role in the chemical reactions of the fiber. For example, the basic groups (hisidine, arginine, and lysine) can attract acid (anionic) dyes, and in addition the side chains of lysine and hisidine are important sites for the attachment of reactive dyes. The sulfur-containing amino acid cysteine plays a very important role, because almost all of the cysteine residues in the fiber are linked in pairs to form cystine residues, which provide a disulfide bridge —S—S— between different polypeptide molecules or between segments of the same molecules as shown ... 

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]. 

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 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 two zinc ions fulfill important but different functions in the DNA-binding domains. The first zinc ion is important for DNA-bindlng because it properly positions the recognition helix the last two cysteine zinc ligands are part of this helix. The second zinc ion is important for dimerization since the five-residue loop between the first two cysteine zinc ligands is the main component of the dimer interaction area. 

The results of this careful design of novel disulfide bridges were very encouraging (Figure 17.4). AH the mutants were more stable in their oxidized forms than wild-type protein. The longer the loop between the cysteine... 

Sanger also determined the sequence of the A chain and identified the cysteine residues involved in disulfide bonds between the A and B chains as well as in the disulfide linkage within the A chain. The complete insulin structure is shown in Figure 27.11. The structure shown is that of bovine insulin (from cattle). The A chains of human insulin and bovine insulin differ in only two amino acid residues then B chains are identical except for the amino acid at the C terminus. 

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