Human ABO(H) Blood Group Glycosyltransferases

Human ABO(H) blood group glycosyltransferases GTA and GTB catalyze the final monosaccharide addition in the biosynthesis of the human A and B blood group antigens.

Introduction

We can categorize our blood types into 4 groups: A, B, AB, & O, on the surface of red blood cells, there are 2 types of antigen: A & B (each type has its own properties) If a blood cell is type A, the surface of the cell contains Antigens for type A and the body will produce antibodies for type B and vice versa for type B. Type AB contains both antigens on the surface and has neither antibodies. Blood type O has no antigens and thus have both A and B antibodies in its system. The A and the B antigens were found to be modified from the carbohydrate corresponding to the O blood group by the addition of different monosaccharides, the A antigen was terminated by the sugar N-acetylgalactosmine (GalNAc) while the B antigen was terminated by galactose. The human ABO(H) blood group antigens are produced by specific glucosyltransferase enzymes (GTs), the ABO blood group system is determined by what type of glucosyltransferases are expressed in the body: N-acetylgalactosaminyltransferase or Galactosyltransferase .

Reaction

An N-acetylgalactosaminyltrasferase (GTA) uses a UDP-GalNac donor to convert the H-antigen acceptor to the A antigen, whereas a galactosyltransferase (GTB) uses UDP-galactose donor to convert the H-antigen acceptor to the B antigen.

Genetics

The ABO gene locus expressing the glycosyltransferases has three main alleleic forms: A, B, and O, the A allele encodes GTA. The B allele encodes GTB, the O allele differs slightly from the A allele by deletion of a single nucleotide. The deletion causes a frameshift and results in translation of an almost entirely different protein that lacks enzymatic activity. This results in H antigen remaining unchanged in case of O groups.

Structural highlights

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Rossmann fold

Structural basis for specifity