2i7b

From Proteopedia

Structure of the naturally occuring mutant of human ABO(H) Blood group B glycosyltransferase: GTB/A268T

PDB ID 2i7b

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Structural highlights

2i7b is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.99Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BGAT_HUMAN This protein is the basis of the ABO blood group system. The histo-blood group ABO involves three carbohydrate antigens: A, B, and H. A, B, and AB individuals express a glycosyltransferase activity that converts the H antigen to the A antigen (by addition of UDP-GalNAc) or to the B antigen (by addition of UDP-Gal), whereas O individuals lack such activity.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

BACKGROUND: Four amino-acid-changing polymorphisms differentiate the blood group A and B alleles. Multiple missense mutations are associated with weak expression of A and B antigens but the structural changes causing subgroups have not been studied. STUDY DESIGN AND METHODS: Individuals or families having serologically weak B antigen on their red cells were studied. Alleles were characterized by sequencing of exons 1 through 7 in the ABO gene. Single crystal X-ray diffraction, three-dimensional-structure molecular modeling, and enzyme kinetics showed the effects of the B allele mutations on the glycosyltransferases. RESULTS: Seven unrelated individuals with weak B phenotypes possessed seven different B alleles, five of which are new and result in substitution of highly conserved amino acids: M189V, I192T, F216I, D262N, and A268T. One of these (F216I) was due to a hybrid allele resulting from recombination between B and O(1v) alleles. The two other alleles were recently described in other ethnic groups and result in V175M and L232P. The first crystal-structure determination (A268T) of a subgroup glycosyltransferase and molecular modeling (F216I, D262N, L232P) indicated conformational changes in the enzyme that could explain the diminished enzyme activity. The effect of three mutations could not be visualized since they occur in a disordered loop. CONCLUSION: The genetic background for B(w) phenotypes is very heterogeneous but usually arises through seemingly random missense mutations throughout the last ABO exon. The targeted amino acid residues, however, are well conserved during evolution. Based on analysis of the resulting structural changes in the glycosyltransferase, the mutations are likely to disrupt molecular bonds of importance for enzymatic function.

Structural basis for red cell phenotypic changes in newly identified, naturally occurring subgroup mutants of the human blood group B glycosyltransferase.,Hosseini-Maaf B, Letts JA, Persson M, Smart E, LePennec PY, Hustinx H, Zhao Z, Palcic MM, Evans SV, Chester MA, Olsson ML Transfusion. 2007 May;47(5):864-75. PMID:17465952^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hosseini-Maaf B, Letts JA, Persson M, Smart E, LePennec PY, Hustinx H, Zhao Z, Palcic MM, Evans SV, Chester MA, Olsson ML. Structural basis for red cell phenotypic changes in newly identified, naturally occurring subgroup mutants of the human blood group B glycosyltransferase. Transfusion. 2007 May;47(5):864-75. PMID:17465952 doi:10.1111/j.1537-2995.2007.01203.x