Roles of Specific Peptides in Enzymes

Specific Peptides (SPs) have been shown [22] to specify the functions of 93% of the enzymes on which they occur. In this work we will focus on the biological importance and possible roles of SPs in the realisation of enzymatic functions. SPs are shown to provide correct functional classification in problems where conventional methods, based on sequence or structure similarity, fail. These cases include enzymatic functions that diverged or converged with evolution. Analysing the coverage of functional annotations of enzymes, we demonstrate that SPs contain major fractions of all annotated biological features. One such feature, DNA binding, is further analysed and observed to show interesting coverage patterns. Moreover, its SPs allow for sub-classification of the species which possess this function into phylogenetic classes. An analysis of sites which have been experimentally altered by mutagenesis leads to the conclusion that SPs contain much more sites that affect the enzyme’s function when mutated than a background model, hence are highly important to enzymatic functions. Events of SPs occurring in three-dimensional pockets of active sites (and other sites of functional importance) are found to be statistically significant. These SPs may play important roles in bringing about the enzymatic function, mostly unknown so far. These SPs are shown to be significantly enriched by glycine, thus leading to the hypothesis that they are responsible for the induced-fit mechanism.