A sequence-coupled vector-projection model for predicting the specificity of GalNAc-transferase.

The specificity of GalNAc-transferase is consistent with the existence of an extended site composed of nine subsites, denoted by R4, R3, R2, R1, R0, R1', R2', R3', and R4', where the acceptor at R0 is either Ser or Thr to which the reducing monosaccharide is being anchored. To predict whether a peptide will react with the enzyme to form a Ser- or Thr-conjugated glycopeptide, a new method has been proposed based on the vector-projection approach as well as the sequence-coupled principle. By incorporating the sequence-coupled effect among the subsites, the interaction mechanism among subsites during glycosylation can be reflected and, by using the vector projection approach, arbitrary assignment for insufficient experimental data can be avoided. The very high ratio of correct predictions versus total predictions for the data in both the training and the testing sets indicates that the method is self-consistent and efficient. It provides a rapid means for predicting O-glycosylation and designing effective inhibitors of GalNAc-transferase, which might be useful for targeting drugs to specific sites in the body and for enzyme replacement therapy for the treatment of genetic disorders.