Peptide aptamer scaffolds are typically small, ordered, soluble proteins. The first scaffold, which is still widely used, is Escherichia coli thioredoxin, the "trxA" gene product (TrxA). In these molecules, a single peptide of variable sequence is displayed instead of the Gly-Pro motif in the TrxA -Cys-Gly-Pro-Cys- active site loop. Improvements to TrxA include substitution of serines for the flanking cysteines, which prevents possible formation of a disulfide bond at the base of the loop, introduction of a D26A substitution to reduce oligomerization, and optimization of codons for expression in human cells. Reviews in 2015 have reported studies using 12 and 20 other scaffolds.