Conclusion ERp18
It has been suggested that the ERp18 protein is unique to multi-celluar organisms and in that group is quite highly conserved. What also may be concluded is that the ERp18 is part of a unique family of proteins which belongs to a larger 'super family' of thioredoxin proteins and contains the specific active site motif CGAC motif. Further analysis is needed to dertermine proteins containing the CXXC active motif have a common ancestor, or if the motif has evolved convergently in several classes of protein. Structural analysis supported ERp18's classification as a thioredoxin protein. 3D modelling identified a catalytic site pertaining to an area of high evolutionary conservation. This catalytic site contained a CXXC residue motif - ubiquitous of all thioredoxin proteins. Furthermore, binding pockets were identified at the catalytic site by several bioinformatics programs. A DALI search identified numerous thioredoxin and thioredoxin-like proteins as being structurally similar, supporting the classification of ERp18 as a thioredoxin. Furthermore, information about the conformation and folding of ERp18 identified a thioredoxin fold. Recent literature has identified ERp18 as a dimer with a single protein molecular weight of 16.4 kDa, leading to the renaming of ERp18 as ERp16. In vitro study of ERp18 suggests ERp18 to be a thiosulfide oxidoreductase involved in the inhibition of stress related apoptosis. It was found to be a member of the thioredoxin superfamily; however, the unique CGAC active site motif sees the protein independent of the existing superfamily groups. The stability of ERp18 in its reduced form indicates that it is involved more so in the oxidation, or forming of disulfide bonds, than in the reduction. Further in vivo studies should be conducted to help determine the exact function of this novel protein. We propose that ERp18 represents a new subfamily of the thioredoxin superfamily. To establish this, it would be beneficial to identify other ER thioredoxin-like proteins that contain the CGAC active site motif.
