Enzymatic activity in disordered states of proteins

Although disordered proteins are able to carry out a variety of different functions, particularly those involved in signalling and regulation, they have been observed to perform catalysis only in a small number of cases. The presence of structural disorder is indeed expected to be poorly compatible with enzymatic catalysis, which requires a well-organised environment in the active site of the enzyme in order to facilitate the formation of the transition state of the chemical reaction to be catalysed. Despite this stringent requirement, current evidence suggests that certain partially disordered proteins could be catalytically active by becoming structured in the regions of their active sites, even if their overall states retain a significant degree of conformational heterogeneity. This type of mechanism, however, does not appear to be not very common, perhaps because the time required to the conformational search within a disordered state to establish a catalytic environment in the presence of the substrate should not be longer than the overall turnover time required for optimal function. In addition, the catalytic environment should be maintained for long enough despite the structural fluctuations to enable the catalytic reaction to take place. As some partially unstructured proteins have been reported to be capable of overcoming these severe limitations and act as enzymes, their study can increase our general understanding of the mechanism of enzymatic catalysis, as well as extend our ability to control the range of functions that can be performed by disordered proteins.