2o1f: Difference between revisions
New page: left|200px<br /> <applet load="2o1f" size="450" color="white" frame="true" align="right" spinBox="true" caption="2o1f, resolution 1.99Å" /> '''Natural Occuring Mu... |
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caption="2o1f, resolution 1.99Å" /> | caption="2o1f, resolution 1.99Å" /> | ||
'''Natural Occuring Mutation of Human ABO(H) galactosyltransferase: GTB/M214R'''<br /> | '''Natural Occuring Mutation of Human ABO(H) galactosyltransferase: GTB/M214R'''<br /> | ||
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==Overview== | ==Overview== | ||
Human blood group A and B antigens are produced by two closely related, glycosyltransferase enzymes. An N-acetylgalactosaminyltransferase (GTA), utilizes UDP-GalNAc to extend H antigen acceptors (Fuc alpha(1-2)Gal, beta-OR) producing A antigens, whereas a galactosyltransferase (GTB), utilizes UDP-Gal as a donor to extend H structures producing B antigens., GTA and GTB have a characteristic (211)DVD(213) motif that coordinates to, a Mn(2+) ion shown to be critical in donor binding and catalysis. Three, GTB mutants, M214V, M214T, and M214R, with alterations adjacent to the, (211)DVD(213) motif have been identified in blood banking laboratories., From serological phenotyping, individuals with the M214R mutation show the, B(el) variant expressing very low levels of B antigens, whereas those with, M214T and M214V mutations give rise to A(weak)B phenotypes. Kinetic, analysis of recombinant mutant GTB enzymes revealed that M214R has a, 1200-fold decrease in k(cat) compared with wild type GTB. The crystal, structure of M214R showed that DVD motif coordination to Mn(2+) was, disrupted by Arg-214 causing displacement of the metal by a water, molecule. Kinetic characterizations of the M214T and M214V mutants, revealed they both had GTA and GTB activity consistent with the serology., The crystal structure of the M214T mutant showed no change in DVD, coordination to Mn(2+). Instead a critical residue, Met-266, which is, responsible for determining donor specificity, had adopted alternate, conformations. The conformation with the highest occupancy opens up the, active site to accommodate the larger A-specific donor, UDP-GalNAc, accounting for the dual specificity. | Human blood group A and B antigens are produced by two closely related, glycosyltransferase enzymes. An N-acetylgalactosaminyltransferase (GTA), utilizes UDP-GalNAc to extend H antigen acceptors (Fuc alpha(1-2)Gal, beta-OR) producing A antigens, whereas a galactosyltransferase (GTB), utilizes UDP-Gal as a donor to extend H structures producing B antigens., GTA and GTB have a characteristic (211)DVD(213) motif that coordinates to, a Mn(2+) ion shown to be critical in donor binding and catalysis. Three, GTB mutants, M214V, M214T, and M214R, with alterations adjacent to the, (211)DVD(213) motif have been identified in blood banking laboratories., From serological phenotyping, individuals with the M214R mutation show the, B(el) variant expressing very low levels of B antigens, whereas those with, M214T and M214V mutations give rise to A(weak)B phenotypes. Kinetic, analysis of recombinant mutant GTB enzymes revealed that M214R has a, 1200-fold decrease in k(cat) compared with wild type GTB. The crystal, structure of M214R showed that DVD motif coordination to Mn(2+) was, disrupted by Arg-214 causing displacement of the metal by a water, molecule. Kinetic characterizations of the M214T and M214V mutants, revealed they both had GTA and GTB activity consistent with the serology., The crystal structure of the M214T mutant showed no change in DVD, coordination to Mn(2+). Instead a critical residue, Met-266, which is, responsible for determining donor specificity, had adopted alternate, conformations. The conformation with the highest occupancy opens up the, active site to accommodate the larger A-specific donor, UDP-GalNAc, accounting for the dual specificity. | ||
==About this Structure== | ==About this Structure== | ||
2O1F 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:// | 2O1F 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=2O1F OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: gtb]] | [[Category: gtb]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:03:46 2008'' | ||
Revision as of 16:03, 23 January 2008
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Natural Occuring Mutation of Human ABO(H) galactosyltransferase: GTB/M214R
OverviewOverview
Human blood group A and B antigens are produced by two closely related, glycosyltransferase enzymes. An N-acetylgalactosaminyltransferase (GTA), utilizes UDP-GalNAc to extend H antigen acceptors (Fuc alpha(1-2)Gal, beta-OR) producing A antigens, whereas a galactosyltransferase (GTB), utilizes UDP-Gal as a donor to extend H structures producing B antigens., GTA and GTB have a characteristic (211)DVD(213) motif that coordinates to, a Mn(2+) ion shown to be critical in donor binding and catalysis. Three, GTB mutants, M214V, M214T, and M214R, with alterations adjacent to the, (211)DVD(213) motif have been identified in blood banking laboratories., From serological phenotyping, individuals with the M214R mutation show the, B(el) variant expressing very low levels of B antigens, whereas those with, M214T and M214V mutations give rise to A(weak)B phenotypes. Kinetic, analysis of recombinant mutant GTB enzymes revealed that M214R has a, 1200-fold decrease in k(cat) compared with wild type GTB. The crystal, structure of M214R showed that DVD motif coordination to Mn(2+) was, disrupted by Arg-214 causing displacement of the metal by a water, molecule. Kinetic characterizations of the M214T and M214V mutants, revealed they both had GTA and GTB activity consistent with the serology., The crystal structure of the M214T mutant showed no change in DVD, coordination to Mn(2+). Instead a critical residue, Met-266, which is, responsible for determining donor specificity, had adopted alternate, conformations. The conformation with the highest occupancy opens up the, active site to accommodate the larger A-specific donor, UDP-GalNAc, accounting for the dual specificity.
About this StructureAbout this Structure
2O1F is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structural effects of naturally occurring human blood group B galactosyltransferase mutations adjacent to the DXD motif., Persson M, Letts JA, Hosseini-Maaf B, Borisova SN, Palcic MM, Evans SV, Olsson ML, J Biol Chem. 2007 Mar 30;282(13):9564-70. Epub 2007 Jan 26. PMID:17259183
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