8d0q
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8d0q]] 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=8D0Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D0Q FirstGlance]. <br> | <table><tr><td colspan='2'>[[8d0q]] 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=8D0Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8D0Q FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6CK:[( | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.39Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6CK:[[(2~{R},3~{S},4~{R},5~{R})-5-(2-azanyl-6-oxidanylidene-1~{H}-purin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]+[(2~{R},3~{S},4~{R},5~{S},6~{R})-3,4,5-tris(oxidanyl)-6-(trifluoromethyl)oxan-2-yl]+hydrogen+phosphate'>6CK</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=8d0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d0q OCA], [https://pdbe.org/8d0q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d0q RCSB], [https://www.ebi.ac.uk/pdbsum/8d0q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d0q ProSAT]</span></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=8d0q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8d0q OCA], [https://pdbe.org/8d0q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8d0q RCSB], [https://www.ebi.ac.uk/pdbsum/8d0q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8d0q ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [https://www.uniprot.org/uniprot/FUT9_HUMAN FUT9_HUMAN] Catalyzes | + | [https://www.uniprot.org/uniprot/FUT9_HUMAN FUT9_HUMAN] Catalyzes alpha(1->3) linkage of fucosyl moiety transferred from GDP-beta-L-fucose to N-acetyl glucosamine (GlcNAc) within type 2 lactosamine (LacNAc, beta-D-Gal-(1->4)-beta-D-GlcNAc-) glycan attached to glycolipids and N- or O-linked glycoproteins. Fucosylates distal type 2 LacNAc and its fucosylated (H-type 2 LacNAc) and sialylated (sialyl-type 2 LacNAc) derivatives to form Lewis x (Lex) (CD15) and Lewis y (Ley) antigenic epitopes involved in cell adhesion and differentiation (PubMed:10386598, PubMed:10622713, PubMed:11278338, PubMed:12107078, PubMed:16282604, PubMed:17335083, PubMed:18395013, PubMed:23192350, PubMed:23263199, PubMed:29593094, PubMed:37202521). Generates Lex epitopes in the brain, presumably playing a role in the maintenance of neuronal stemness and neurite outgrowth in progenitor neural cells (By similarity) (PubMed:17335083, PubMed:23000574). Fucosylates the internal type 2 LacNAc unit of the polylactosamine chain to form VIM-2 antigen that serves as recognition epitope for SELE (PubMed:23192350). Can also modify milk oligosaccharides, in particular type 2 tetrasaccharide LNnT (PubMed:37202521).[UniProtKB:O88819]<ref>PMID:10386598</ref> <ref>PMID:10622713</ref> <ref>PMID:11278338</ref> <ref>PMID:12107078</ref> <ref>PMID:16282604</ref> <ref>PMID:17335083</ref> <ref>PMID:18395013</ref> <ref>PMID:23000574</ref> <ref>PMID:23192350</ref> <ref>PMID:23263199</ref> <ref>PMID:29593094</ref> <ref>PMID:37202521</ref> |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Mammalian cell surface and secreted glycoproteins exhibit remarkable glycan structural diversity that contributes to numerous physiological and pathogenic interactions. Terminal glycan structures include Lewis antigens synthesized by a collection of alpha1,3/4-fucosyltransferases (CAZy GT10 family). At present, the only available crystallographic structure of a GT10 member is that of the Helicobacter pylori alpha1,3-fucosyltransferase, but mammalian GT10 fucosyltransferases are distinct in sequence and substrate specificity compared with the bacterial enzyme. Here, we determined crystal structures of human FUT9, an alpha1,3-fucosyltransferase that generates Lewis(x) and Lewis(y) antigens, in complex with GDP, acceptor glycans, and as a FUT9-donor analog-acceptor Michaelis complex. The structures reveal substrate specificity determinants and allow prediction of a catalytic model supported by kinetic analyses of numerous active site mutants. Comparisons with other GT10 fucosyltransferases and GT-B fold glycosyltransferases provide evidence for modular evolution of donor- and acceptor-binding sites and specificity for Lewis antigen synthesis among mammalian GT10 fucosyltransferases. | Mammalian cell surface and secreted glycoproteins exhibit remarkable glycan structural diversity that contributes to numerous physiological and pathogenic interactions. Terminal glycan structures include Lewis antigens synthesized by a collection of alpha1,3/4-fucosyltransferases (CAZy GT10 family). At present, the only available crystallographic structure of a GT10 member is that of the Helicobacter pylori alpha1,3-fucosyltransferase, but mammalian GT10 fucosyltransferases are distinct in sequence and substrate specificity compared with the bacterial enzyme. Here, we determined crystal structures of human FUT9, an alpha1,3-fucosyltransferase that generates Lewis(x) and Lewis(y) antigens, in complex with GDP, acceptor glycans, and as a FUT9-donor analog-acceptor Michaelis complex. The structures reveal substrate specificity determinants and allow prediction of a catalytic model supported by kinetic analyses of numerous active site mutants. Comparisons with other GT10 fucosyltransferases and GT-B fold glycosyltransferases provide evidence for modular evolution of donor- and acceptor-binding sites and specificity for Lewis antigen synthesis among mammalian GT10 fucosyltransferases. | ||
| - | Structural basis for Lewis antigen synthesis by the alpha1,3-fucosyltransferase FUT9.,Kadirvelraj R, Boruah BM, Wang S, Chapla D, Huang C, Ramiah A, Hudson KL, Prudden AR, Boons GJ, Withers SG, Wood ZA, Moremen KW Nat Chem Biol. 2023 | + | Structural basis for Lewis antigen synthesis by the alpha1,3-fucosyltransferase FUT9.,Kadirvelraj R, Boruah BM, Wang S, Chapla D, Huang C, Ramiah A, Hudson KL, Prudden AR, Boons GJ, Withers SG, Wood ZA, Moremen KW Nat Chem Biol. 2023 Aug;19(8):1022-1030. doi: 10.1038/s41589-023-01345-y. Epub , 2023 May 18. PMID:37202521<ref>PMID:37202521</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Human FUT9 bound to GDP-CF3-Fucose and H-Type 2
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