Glycosyltransferase A + UDP + H antigen acceptor

The ABO blood type is determined by a single gene. Blood type A individuals have a gene to encode for the enzyme glycosyltransferase A (GTA). For blood type B individuals, the gene encodes the enzyme GTB. Blood type O does not have either gene. GTA and GTB are very similar, but their slight differences can cause life or death consequences for patients receiving a blood transfusions.

https://www.youtube.com/watch?v=WtDDfVY-79g

ABO blood types are sugars. GTA uses a donor to convert the H antigen disaccharide acceptor into the A antigen. This means that it adds one extra sugar, specifically an N-acetylgalactosamine to the H antigen carbohydrate chain. This creates a modified H antigen. This concept is similar to that of the B antigen except that GTB is used along with a different donor to add galactose and modify the H antigen as well. Blood type O only has the H antigen that is not modified. Blood type AB has genes for both GTA and GTB.

UDP

GTA uses a uridine diphosphate N-acetylgalactosamine (UDP-GalNAc) to convert the H antigen into the A antigen while GTB uses a UDP-galactose donor to convert the H antigen into the B antigen.

Primary Structure

The primary structure of Glycosyltransferase A+UDP+H antigen is composed of 264 residues.

Secondary Structure

The secondary structure of Glycosyltransferase A+UDP+H antigen is 27% helical (11 helices; 8 residues) and 18% beta sheet (17 strands; 55 residues). The loop portion of the molecule is protein that does not have secondary structure.

GTA contains an N-terminal domain and a C-termianl domain which are separated by a cleft containing the active site. The N-terminal is the portion of GTA that recognizes the donor while the C-terminal is the portion that contains the disaccharide acceptor binding site.

4 Critical Amino Acids

GTA differs from GTB by four critical amino acid residue positions. In GTA the four residue positions are Arginine (Arg) 176, Glycine (Gly) 235, Leucine (Leu) 266, and Glycine (Gly) 268. All four residues are found in the central cleft. Arg 176 is furthest from the binding site. Gly 235 forces the tail of the H antigen to assume different conformations in GTA versus GTB. Leu 266 and Gly 268 occupy positions at the active site and make contact with the UDP-GalNAc donor. Leu 266 is the dominating residue while Gly 268 has a lesser effect. Leu 266 contacts the acetamido/hydroxyl groups of the donor groups and distinguishes between them. There is complementary interaction between the larger acetamido group in UDP-GalNAc and the smaller Leu 266 residue. This is the opposite in GTB, which contains a smaller donor and a larger residue. Guy 268 has a lesser effect that Leu 266 because it can only contact parts that are identical in the corresponding donor. GTA also has Histidine (His) 233 that can form a hydrogen bond with the acetamido group in UDP-GalNAc so it can be positioned.

More information regarding enzyme specificity: GTA has a lower floor of active site cleft, meaning that is has a larger active site cleft. This is the opposite for GTB. The smaller active site cleft of GTB does not allow for UDP-GalNAc The smaller donor corresponding to GTB can fit in the GTA active site cleft, but complementary interactions will not form.

FUC (Part of H antigen acceptor)

References:
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http://www.nature.com/nsmb/journal/v9/n9/images/nsb832F3.gif

https://upload.wikimedia.org/wikipedia/commons/thumb/c/ce/ABO_blood_ group_diagram.svg/2000px ABO_blood_group_ diagram.svg.png

Patenaude, S. I., Seto, N. O.L., Borisova, S. N., Szpacenko, A., Marcus, S. L., Palcic, M. M., & Evans, S. V. (2002). The structural basis for specificity in human ABO(H) blood group biosynthesis. Nature Structural & Molecular Biology, 9, 685-690. http://dx.doi.org/10.1038/nsb832