A Proactive Role of Water Molecules in Acceptor Recognition by Protein O-Fucosyltransferase 2
Protein O-fucosyltransferase 2 (POFUT2) is an essential enzyme that fucosylates serine and threonine residues of folded thrombospondin type 1 repeats (TSRs). To date, the mechanism by which this enzyme recognizes very dissimilar TSRs has been unclear. The crystal structure of Caenorhabditis elegans POFUT2 (CePOFUT2) in complex with GDP and human TSR1 which is reported at 2.0 Ang. resolution illuminates mechanistic features of the glycosylation reaction. The combined use of crystallographic and mutagenesis data, together with atomic-level simulations and computation of the spatial distribution functions for water molecules, uncover the binding mechanism which involves a dynamic network of water-mediated interactions.
The results described in the article might have a broader significance in our understanding on how some enzymes have the plasticity to modify a wide variety of peptide sequences throughout the active participation of highly structured water molecules.