Thioredoxins are general protein reductants and regulate the activity of other enzymes by reducing disulfides. The thioredoxin fold is a distinct structural motif with a four-stranded beta-sheet and three flanking alpha-helices. The fold includes an N-terminal beta alpha beta motif and a C-terminal beta beta alpha motif connected by a loop of residues which includes a third helix. Some of the proteins with the thioredoxin fold have a Cys-X-X-Cys active site motif. The beta-strands in the N-terminal motif run parallel while those from the C-terminal motif run antiparallel. The alpha-helices of the N- and C-terminal motifs line up parallel on one side of the sheet. The alpha-helix connecting the N- and C-terminal motifs is located on the opposite side of the beta-sheet to the other two helices and is perpendicular to them.
This is the pdb file (2trx.pdb) of thioredoxin from E. coli which has been studied extensively. Chain A and chain B consists of 108 residues and the typical thioredoxin fold. However, this comparison will focus on the similarities between thioredoxin-2 from Anabaena and chain A of AaFd4.
Press this button to show the pdb file (1thx.pdb) of thioredoxin-2 from Anabaena (Trx-2).
This protein consists of a single chain. Trx-2 has 108 residues, a 5 stranded beta-sheet core, 5 helices, 9 beta turns, a beta bulge, a beta hairpin, a beta alpha beta unit, a psi-loop, and a disulphide bridge. The active site includes a conserved disulfide ring (31WCGPC35).
Chain A of AaFd4 and Trx-2 are superimposed showing the similarity between the folds. The first four beta-strands and the helices of AaFd4 take on the thioredoxin-like fold, but AaFd4 also includes a fifth beta-strand that extends to one edge of the thioredoxin fold.
In addition, the cysteine ligands of AaFd4 Cys9 and Cys22 are in similar positions to those of the active-site cysteine residues, Cys32 and Cys35 in Trx-2. Placement of cysteine residues between beta-strand 1 and alpha-helix 1 of the thioredoxin fold is common, and the residues in these positions are catalytically important. Thioredoxin has been used as a protein design platform to incorporate novel metallocenters into proteins. One such design resulted in the inclusion of a mononuclear iron-sulfer center at the active-site disulfide bridge of thioredoxin.
AaFd4 also has a cis-proline residue (Pro63) between alpha-helix 2 and beta-strand 3 which is similar to thioredoxins.