Thioredoxin, domain structure

Fig. 3. The crystal structure of DsbC. DsbC forms a V-shaped homodimer. The monomer consists of a C-terminal thioredoxin domain and an N-terminal dimerization domain. The two domains are joined via a linker helix. The monomers interact via two consecutive /3-strands, which form two extended /3-sheets in the dimer.

Figure 6.8 Schematic diagram of the enzyme DsbA which catalyzes disulfide bond formation and rearrangement. The enzyme is folded into two domains, one domain comprising five a helices (green) and a second domain which has a structure similar to the disulfide-containing redox protein thioredoxin (violet). The N-terminal extension (blue) is not present in thioredoxin. (Adapted from J.L. Martin et al.. Nature 365 464-468, 1993.)...

Figure 13.16 Schematic diagram of the phosducin molecule. Helices are blue, p strands are red and loop regions are orange. The structure folds into two separate domains, a N-terminal helical domain and a C-terminal domain that has the thioredoxin fold. Some of the loop regions in the helical domain are not well defined. (Adapted from R. Gaudet et al.. Cell 87 577-588, 1996.)...

Protein structure determinations have identified several examples of one domain inserted within another. One example is the E. coli DsbA protein, which catalyzes the formation of disulfide bonds in the periplasm. The enzyme consists of two domains a thioredoxin-like domain that contains the active site, and an inserted helical domain similar to the C-terminal domain of thermolysins (Martin et al., 1993). The inserted domain forms a cap over the active site, suggesting that it plays a role in binding to partially folded polypeptide chains before oxidation of... 

The 2.0-A crystal structure revealed that DsbA contains a thioredoxin-like fold (Martin et al., 1993). The thioredoxin fold includes a central /3-sheet formed by four antiparallel /3-strands. The central /3-sheet is flanked by a perpendicular helix and two helices on the opposite side (Martin, 1995). Compared to thioredoxin, DsbA contains an additional /l-strand in the central (6-sheet and the insertion of a 65-residue helical domain (Fig. 1). Such insertions are commonly observed within the thioredoxin family (Martin, 1995 McCarthy etal., 2000). Most members of the thioredoxin superfamily are involved in disulfide exchange reactions, and contain a redox-active CXXC motif in their active site. The CXXC motif participates in disulfide exchange reactions by going through reversible cycles of oxidation and reduction. In this motif, the... 

Fig. 1. The crystal structure of DsbA. DsbA contains a thioredoxin-like fold including the insertion of an a-helical domain. The arrow indicates the location of the active-site disulfide bond.

A further crystal structure of the C-terminal domain of KaiA and a structure of full-length KaiB from the cyanobacterium Anabaena PPC7120 revealed a thioredoxin-like fold for the latter (Garces et al 2004) (Figure 13-4). This work also identified similarities in the dimensions and electrostatic potentials of particular regions in the KaiA and KaiB dimers as well as similar spacings between conserved arginine pairs on the surfaces of the respective Kai proteins. A crystal structure of... 

In the present context, we are currently studying peptidomimetic polycyclic structures derived from the thioredoxin reductase active site [56,57], which consist of a domain of peptidic nature containing the sequence for the recognition and of a domain of non-peptidic nature. In the present case, this last domain is formed by an unnatural amino acid of the size (i.e. isosteric) of a bi- or tri-peptide that can undergo cis— trans photoisomerization. Such isomerization induces conformational changes in... 

The two thioredoxin-like domains in PDI possess the same active site motif and display obvious sequence identities to each other (50%) and to thioredoxin (30%). However, in Pf PDO the similarities among the two structural units and thioredoxin are only apparent upon the comparison of their three-dimensional structures. As the two Pf PDO units have distinct active site motifs and show rather low sequence identities (<20%) to each other and to thioredoxin, one may assume that the two Pf PDO units might have evolved more divergently than the thioredoxin-like domains in eukaryotic PDI. This assumption, however, is not in line with the hypothesis that hyperthermophiles are the least divergent organisms, which may represent the closest living descendants of ancestral life forms. " As the origin... 

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