2i7b
From Proteopedia
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==Overview== | ==Overview== | ||
| - | BACKGROUND: Four amino-acid-changing polymorphisms differentiate the blood | + | 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. |
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| + | ==Disease== | ||
| + | Known disease associated with this structure: Blood group, ABO system OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=110300 110300]] | ||
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | 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, | + | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17465952 17465952] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Evans, S | + | [[Category: Evans, S V.]] |
| - | [[Category: Letts, J | + | [[Category: Letts, J A.]] |
[[Category: HG]] | [[Category: HG]] | ||
[[Category: abo allele]] | [[Category: abo allele]] | ||
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[[Category: polymorphism]] | [[Category: polymorphism]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:49:58 2008'' |
Revision as of 15:49, 21 February 2008
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Structure of the naturally occuring mutant of human ABO(H) Blood group B glycosyltransferase: GTB/A268T
Contents |
Overview
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.
Disease
Known disease associated with this structure: Blood group, ABO system OMIM:[110300]
About this Structure
2I7B is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
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
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