2o1f
From Proteopedia
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[[Image:2o1f.gif|left|200px]] | [[Image:2o1f.gif|left|200px]] | ||
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| - | + | {{STRUCTURE_2o1f| PDB=2o1f | SCENE= }} | |
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'''Natural Occuring Mutation of Human ABO(H) galactosyltransferase: GTB/M214R''' | '''Natural Occuring Mutation of Human ABO(H) galactosyltransferase: GTB/M214R''' | ||
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[[Category: Evans, S V.]] | [[Category: Evans, S V.]] | ||
[[Category: Letts, J A.]] | [[Category: Letts, J A.]] | ||
| - | [[Category: | + | [[Category: Blood group subtypes. naturally occurring mutation]] |
| - | [[Category: | + | [[Category: Dxd]] |
| - | [[Category: | + | [[Category: Glycosytransferase]] |
| - | [[Category: | + | [[Category: Gtb]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:11:23 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 07:11, 4 May 2008
Natural Occuring Mutation of Human ABO(H) galactosyltransferase: GTB/M214R
Contents |
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.
Disease
Known disease associated with this structure: Blood group, ABO system OMIM:[110300]
About this Structure
2O1F is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Sun May 4 10:11:23 2008
