An Atlas of the Thioredoxin Fold Class Reveals the Complexity of Function-Enabling Adaptations
Figure 2
Most Trx fold active sites involve catalytic cysteines.
A A topological diagram of the Trx fold, showing the four-stranded mixed beta sheet sandwiched by three alpha helices. The archetypal CxxC active site cysteines from thioredoxin are represented by yellow bars near the N-terminus of the first alpha helix. Also shown are common locations for insertions and extensions relative to the Trx fold (dashes), and the position of a cis-proline that is frequently found at the N-terminus of the third beta strand. A grey box denotes the region of the fold shown in C–E. Active site types are abbreviated using a motif like “CxxC”, where a ‘C’ indicates presence of a cysteine, and ‘c’ indicates the presence of some residue other than cysteine. “CxxxC” means the active site cysteines are separated by three amino acids. B The classic CxxC active site, illustrated by human Trx 2 (PDB:1UVZ); Cys 31 and Cys 34 are shown. A grey box denotes the corresponding region of the fold shown in C–E. C The Cxxc active site, where the second cysteine has been mutated to another residue, illustrated by E. coli ArsC (PDB:1I9D); Cys 12 is shown (active site: CxxS). D The cxxC active site, in which the N-terminal Trx Cys has been lost, illustrated by human peroxiredoxin 5 (PDB:1OC3); Cys 47 is shown (active site: TxxC). E The CxxxC active site, in which the N-terminal Cys has been shifted further into the loop between the first beta strand and alpha helix, illustrated by S. cerevisiae SCO1 (PDB:2B7J); a disulfide bond between Cys 148 and Cys 152 is shown.