2i7b
From Proteopedia
(New page: 200px<br /> <applet load="2i7b" size="450" color="white" frame="true" align="right" spinBox="true" caption="2i7b, resolution 1.99Å" /> '''Structure of the na...) |
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caption="2i7b, resolution 1.99Å" /> | caption="2i7b, resolution 1.99Å" /> | ||
'''Structure of the naturally occuring mutant of human ABO(H) Blood group B glycosyltransferase: GTB/A268T'''<br /> | '''Structure of the naturally occuring mutant of human ABO(H) Blood group B glycosyltransferase: GTB/A268T'''<br /> | ||
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==Overview== | ==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. | 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== | ||
| - | 2I7B is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with HG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2I7B is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=HG:'>HG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I7B OCA]. |
==Reference== | ==Reference== | ||
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[[Category: polymorphism]] | [[Category: polymorphism]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:11:42 2008'' |
Revision as of 13:11, 23 January 2008
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Structure of the naturally occuring mutant of human ABO(H) Blood group B glycosyltransferase: GTB/A268T
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.
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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