The Importance of Disordered Loops in ABO Glycosyltransferases

The human ABO antigens are carbohydrates that differ from each other by the immunodominant sugar. The O phenotype is characterized by the absence of the A- or B-defining carbohydrate. The glycosyltransferases that create the A and B antigens share a considerable amino acid sequence and a structural homology and feature 2 series of amino acids whose exact location within the enzymes' structure cannot be determined. One series is 16 amino acids in length and probably lies next to the catalytic center, whereas less is known about the other 10-amino acid disordered loop located at the C-terminus of the protein. These “disordered” segments of amino acids can be found in other glycosyltransferases from disparate species. The precise role of these amino acids is unclear although recent evidence suggests that they are involved in substrate binding and turnover. A more complete understanding of its function will provide fundamental insights into the activity of glycosyltransferases and a potential target for novel therapeutics in the case of pathogens. In this review, we describe the nature of various disordered regions in glycosyltransferase structures from bacteria to human beings.