PDBsum entry 2i7b

Transferase

PDB id: 2i7b

Contents

Protein chain

262 a.a. *

Metals

_HG ×4

Waters ×186

* Residue conservation analysis

PDB id:

2i7b

Name:

Transferase

Title:

Structure of the naturally occuring mutant of human abo(h) blood group b glycosyltransferase: gtb/a268t

Structure:

Alpha 1-3-galactosyltransferase. Chain: a. Synonym: transferase a, alpha 1-3-n- acetylgalactosaminyltransferase. Transferase b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: abo. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Resolution:

1.99Å R-factor: 0.187 R-free: 0.231

Authors:

J.A.Letts,S.V.Evans

Key ref:

B.Hosseini-Maaf et al. (2007). Structural basis for red cell phenotypic changes in newly identified, naturally occurring subgroup mutants of the human blood group B glycosyltransferase. Transfusion, 47, 864-875. PubMed id: 17465952

Date:

30-Aug-06 Release date: 22-May-07

Protein chain

P16442  (BGAT_HUMAN) -  Histo-blood group ABO system transferase from Homo sapiens

Seq: 354 a.a.

Struc: 262 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.2.4.1.37 - fucosylgalactoside 3-alpha-galactosyltransferase.
• Reaction: an alpha-L-fucosyl-(1->2)-beta-D-galactosyl derivative + UDP-alpha-D- galactose = an alpha-D-galactosyl-(1->3)-[alpha-L-fucosyl-(1->2)]-beta-D- galactosyl derivative + UDP + H⁺
• Enzyme class 2: E.C.2.4.1.40 - glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase.
• Reaction: an alpha-L-fucosyl-(1->2)-beta-D-galactosyl derivative + UDP-N-acetyl- alpha-D-galactosamine = an N-acetyl-alpha-D-galactosaminyl-(1->3)-[alpha- L-fucosyl-(1->2)]-beta-D-galactosyl derivative + UDP + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

Transfusion 47:864-875 (2007)

PubMed id: 17465952

Structural basis for red cell phenotypic changes in newly identified, naturally occurring subgroup mutants of the human blood group B glycosyltransferase.

B.Hosseini-Maaf, J.A.Letts, M.Persson, E.Smart, P.Y.LePennec, H.Hustinx, Z.Zhao, M.M.Palcic, S.V.Evans, M.A.Chester, M.L.Olsson.

ABSTRACT

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.