DsbA structure

Disulfide bonds in proteins are generally stable and nonreactive, acting like bolts in the structure. However, oxidized DsbA is less stable than the reduced form and its disulfide bond is very reactive. DsbA is thus a strong... 

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.)...

Martin, J.E., Bardwell, J.C.A., Kuriyan, J. Crystal structure of the DsbA protein required for disulphide bond formation in vivo. Nature 365 464-468, 1993. 

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... 

Guddat, L. W., Bardwell,J. C., andMartin.J. L. (1998). Crystal structures of reduced and oxidized DsbA investigation of domain motion and thiolate stabilization. Structure, 6, 757-767. 

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 potential substrate binding site of DsbA has been deduced from its crystal structure (Guddat et al., 1997b) however, no structure of a... 

In DsbA, 75 residues, including maiidy the whole a-helical domain, are excluded in structural superposition and sequence identity calculation. 

Unlike thioredoxin, glutaredoxin, and DsbA, which possess only one thiore-doxin-like motif, P/PDO is the first protein disulfide oxidoreductase whose three-dimensional structure has been shown to contain two thioredoxin fold motifs with two active sites. Thus, P/PDO shows structural resemblance to PDI and PDI-like protein s. This structural feature suggests that P/PDO is probably not just a simple protein disulfide reductant like thioredoxin as described previously. It may belong to the growing family of PDI-like proteins. From a structural point of view, P/PDO may represent the simplest form of PDI. 

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