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| | <StructureSection load='6x5u' size='340' side='right'caption='[[6x5u]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='6x5u' size='340' side='right'caption='[[6x5u]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6x5u]] is a 8 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=6X5U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6X5U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6x5u]] is a 8 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=6X5U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6X5U FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASN:ASPARAGINE'>ASN</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6x5h|6x5h]], [[6x5r|6x5r]], [[6x5s|6x5s]], [[6x5t|6x5t]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASN:ASPARAGINE'>ASN</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FUT8 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=6x5u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x5u OCA], [https://pdbe.org/6x5u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x5u RCSB], [https://www.ebi.ac.uk/pdbsum/6x5u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x5u ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glycoprotein_6-alpha-L-fucosyltransferase Glycoprotein 6-alpha-L-fucosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.68 2.4.1.68] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6x5u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x5u OCA], [http://pdbe.org/6x5u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6x5u RCSB], [http://www.ebi.ac.uk/pdbsum/6x5u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6x5u ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FUT8_HUMAN FUT8_HUMAN]] Catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue, next to the peptide chains in N-glycans.<ref>PMID:9133635</ref> | + | [https://www.uniprot.org/uniprot/FUT8_HUMAN FUT8_HUMAN] Catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue, next to the peptide chains in N-glycans.<ref>PMID:9133635</ref> |
| | <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: Glycoprotein 6-alpha-L-fucosyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kadirvelraj, R]] | + | [[Category: Kadirvelraj R]] |
| - | [[Category: Wood, Z A]] | + | [[Category: Wood ZA]] |
| - | [[Category: Fucosyl transferase]]
| + | |
| - | [[Category: Glycosyl transferase]]
| + | |
| - | [[Category: Gt-b fold]]
| + | |
| - | [[Category: Inverting]]
| + | |
| - | [[Category: Transferase]]
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| Structural highlights
6x5u is a 8 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 3.2Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
FUT8_HUMAN Catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue, next to the peptide chains in N-glycans.[1]
Publication Abstract from PubMed
Mammalian Asn-linked glycans are extensively processed as they transit the secretory pathway to generate diverse glycans on cell surface and secreted glycoproteins. Additional modification of the glycan core by alpha-1,6-fucose addition to the innermost GlcNAc residue (core fucosylation) is catalyzed by an alpha-1,6-fucosyltransferase (FUT8). The importance of core fucosylation can be seen in the complex pathological phenotypes of FUT8 null mice, which display defects in cellular signaling, development, and subsequent neonatal lethality. Elevated core fucosylation has also been identified in several human cancers. However, the structural basis for FUT8 substrate specificity remains unknown. Here, using various crystal structures of FUT8 in complex with a donor substrate analog, and with four distinct glycan acceptors, we identify the molecular basis for FUT8 specificity and activity. The ordering of three active site loops corresponds to an increased occupancy for bound GDP, suggesting an induced-fit folding of the donor binding subsite. Structures of the various acceptor complexes were compared with kinetic data on FUT8 active site mutants and with specificity data from a library of glycan acceptors to reveal how binding site complementarity and steric hindrance can tune substrate affinity. The FUT8 structure was also compared with other known fucosyltransferases to identify conserved and divergent structural features for donor and acceptor recognition and catalysis. These data provide insights into the evolution of modular templates for donor and acceptor recognition among GT-B fold glycosyltransferases in the synthesis of diverse glycan structures in biological systems.
Characterizing human alpha-1,6-fucosyltransferase (FUT8) substrate specificity and structural similarities with related fucosyltransferases.,Boruah BM, Kadirvelraj R, Liu L, Ramiah A, Li C, Zong G, Bosman GP, Yang JY, Wang LX, Boons GJ, Wood ZA, Moremen KW J Biol Chem. 2020 Oct 1. pii: RA120.014625. doi: 10.1074/jbc.RA120.014625. PMID:33004438[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yanagidani S, Uozumi N, Ihara Y, Miyoshi E, Yamaguchi N, Taniguchi N. Purification and cDNA cloning of GDP-L-Fuc:N-acetyl-beta-D-glucosaminide:alpha1-6 fucosyltransferase (alpha1-6 FucT) from human gastric cancer MKN45 cells. J Biochem. 1997 Mar;121(3):626-32. PMID:9133635
- ↑ Boruah BM, Kadirvelraj R, Liu L, Ramiah A, Li C, Zong G, Bosman GP, Yang JY, Wang LX, Boons GJ, Wood ZA, Moremen KW. Characterizing human alpha-1,6-fucosyltransferase (FUT8) substrate specificity and structural similarities with related fucosyltransferases. J Biol Chem. 2020 Oct 1. pii: RA120.014625. doi: 10.1074/jbc.RA120.014625. PMID:33004438 doi:http://dx.doi.org/10.1074/jbc.RA120.014625
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