2o1h

From Proteopedia

Naturally occurring mutation of Humna ABO(H) Galactosyltransferase in complex with UDP: GTB/M214T_UDP

Structural highlights

2o1h is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.67Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BGAT_HUMAN This protein is the basis of the ABO blood group system. The histo-blood group ABO involves three carbohydrate antigens: A, B, and H. A, B, and AB individuals express a glycosyltransferase activity that converts the H antigen to the A antigen (by addition of UDP-GalNAc) or to the B antigen (by addition of UDP-Gal), whereas O individuals lack such activity.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Persson M, Letts JA, Hosseini-Maaf B, Borisova SN, Palcic MM, Evans SV, Olsson ML. Structural effects of naturally occurring human blood group B galactosyltransferase mutations adjacent to the DXD motif. J Biol Chem. 2007 Mar 30;282(13):9564-70. Epub 2007 Jan 26. PMID:17259183 doi:10.1074/jbc.M610998200