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| | <StructureSection load='5c3d' size='340' side='right'caption='[[5c3d]], [[Resolution|resolution]] 1.39Å' scene=''> | | <StructureSection load='5c3d' size='340' side='right'caption='[[5c3d]], [[Resolution|resolution]] 1.39Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5c3d]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C3D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C3D FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5c3d]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C3D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5C3D FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene>, <scene name='pdbligand=URM:(((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)methyl)phosphonic+(((2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl+phosphoric)+anhydride'>URM</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene>, <scene name='pdbligand=URM:(((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)methyl)phosphonic+(((2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl+phosphoric)+anhydride'>URM</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5bxc|5bxc]], [[5c1g|5c1g]], [[5c1h|5c1h]], [[5c1l|5c1l]], [[5c36|5c36]], [[5c38|5c38]], [[5c3a|5c3a]], [[5c3b|5c3b]], [[5c48|5c48]], [[5c49|5c49]], [[5c4b|5c4b]], [[5c4c|5c4c]], [[5c4d|5c4d]], [[5c4e|5c4e]], [[5c4f|5c4f]], [[5c47|5c47]], [[5c8r|5c8r]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5c3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c3d OCA], [https://pdbe.org/5c3d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5c3d RCSB], [https://www.ebi.ac.uk/pdbsum/5c3d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5c3d ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ABO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5c3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c3d OCA], [http://pdbe.org/5c3d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5c3d RCSB], [http://www.ebi.ac.uk/pdbsum/5c3d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5c3d ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BGAT_HUMAN 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. | + | [https://www.uniprot.org/uniprot/BGAT_HUMAN 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Borisova, S]] | + | [[Category: Borisova S]] |
| - | [[Category: Evans, S V]] | + | [[Category: Evans SV]] |
| - | [[Category: Gagnon, S]] | + | [[Category: Gagnon S]] |
| - | [[Category: Haji-Ghassemi, O]] | + | [[Category: Haji-Ghassemi O]] |
| - | [[Category: Johal, A R]] | + | [[Category: Johal AR]] |
| - | [[Category: Lowary, T L]] | + | [[Category: Lowary TL]] |
| - | [[Category: Meloncelli, P]] | + | [[Category: Meloncelli P]] |
| - | [[Category: Zheng, R B]] | + | [[Category: Zheng RB]] |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
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.
Publication Abstract from PubMed
Homologous glycosyltransferases GTA and GTB catalyze the final step in ABO(H) blood group A and B antigen synthesis through sugar transfer from activated donor to the H antigen acceptor. These enzymes have a GT-A-fold-type with characteristic mobile polypeptide loops that cover the active site upon substrate binding and, despite intense investigation, many aspects of substrate specificity and catalysis remain unclear. The structures of GTA, GTB, and their chimeras have been determined to between 1.55 and 1.39 A resolution in complex with natural donors UDP-Gal, UDP-Glc and, in an attempt to overcome one of the common problems associated with three-dimensional studies, the non-hydrolysable donor analog UDP-phosphono-galactose (UDP-C-Gal). While the uracil moieties of the donors are observed to maintain a constant location, the sugar moieties lie in four distinct conformations varying from extended to the 'tucked under' conformation associated with catalysis, each stabilized by different hydrogen bonding partners with the enzyme. Further, several structures show clear evidence that the donor sugar is disordered over two of the observed conformations and so provide evidence for step-wise insertion into the active site. However, while the natural donors can both assume the tucked under conformation in complex with enzyme, UDP-C-Gal cannot. While UDP-C-Gal was designed to be 'isosteric' with natural donor, the small differences in structure imposed by changing the epimeric oxygen atom to carbon appear to render the enzyme incapable of binding the analog in the active conformation, and so preclude its use as a substrate mimic in GTA and GTB.
High resolution structures of the human ABO(H) blood group enzymes in complex with donor analogs reveal that the enzymes utilize multiple donor conformations to bind substrates in a step-wise manner.,Gagnon SM, Meloncelli PJ, Zheng RB, Haji-Ghassemi O, Johal AR, Borisova SN, Lowary TL, Evans SV J Biol Chem. 2015 Sep 15. pii: jbc.M115.682401. PMID:26374898[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gagnon SM, Meloncelli PJ, Zheng RB, Haji-Ghassemi O, Johal AR, Borisova SN, Lowary TL, Evans SV. High resolution structures of the human ABO(H) blood group enzymes in complex with donor analogs reveal that the enzymes utilize multiple donor conformations to bind substrates in a step-wise manner. J Biol Chem. 2015 Sep 15. pii: jbc.M115.682401. PMID:26374898 doi:http://dx.doi.org/10.1074/jbc.M115.682401
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