|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6vld' size='340' side='right'caption='[[6vld]], [[Resolution|resolution]] 2.28Å' scene=''> | | <StructureSection load='6vld' size='340' side='right'caption='[[6vld]], [[Resolution|resolution]] 2.28Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6vld]] is a 4 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=6VLD OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VLD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vld]] is a 4 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=6VLD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VLD 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=SO4:SULFATE+ION'>SO4</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]] 2.28Å</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='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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6vld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vld OCA], [https://pdbe.org/6vld PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vld RCSB], [https://www.ebi.ac.uk/pdbsum/6vld PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vld ProSAT]</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=6vld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vld OCA], [http://pdbe.org/6vld PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vld RCSB], [http://www.ebi.ac.uk/pdbsum/6vld PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vld 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 == |
| Line 24: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glycoprotein 6-alpha-L-fucosyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dramicanin, M]] | + | [[Category: Dramicanin M]] |
| - | [[Category: Goddard-Borger, E D]] | + | [[Category: Goddard-Borger ED]] |
| - | [[Category: Jarva, M A]] | + | [[Category: Jarva MA]] |
| - | [[Category: John, A]] | + | [[Category: John A]] |
| - | [[Category: Lingford, J P]] | + | [[Category: Lingford JP]] |
| - | [[Category: Mao, R]] | + | [[Category: Mao R]] |
| - | [[Category: Core fucose]]
| + | |
| - | [[Category: Fucosyltransferase]]
| + | |
| - | [[Category: Fut8]]
| + | |
| - | [[Category: Glycosyltransferase]]
| + | |
| - | [[Category: N-glycan]]
| + | |
| - | [[Category: Sh3 domain]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
6vld is a 4 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 2.28Å |
| 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
Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans. This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder. The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown. Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80-2.50 A resolution. These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis. Together with molecular dynamics simulations, the structures also revealed how FUT8 dimerization plays an important role in defining the acceptor substrate-binding site. Collectively, this information significantly builds on our understanding of the core fucosylation process.
Structural basis of substrate recognition and catalysis by fucosyltransferase 8.,Jarva MA, Dramicanin M, Lingford JP, Mao R, John A, Jarman KE, Grinter R, Goddard-Borger ED J Biol Chem. 2020 May 8;295(19):6677-6688. doi: 10.1074/jbc.RA120.013291. Epub, 2020 Mar 27. PMID:32220931[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
- ↑ Jarva MA, Dramicanin M, Lingford JP, Mao R, John A, Jarman KE, Grinter R, Goddard-Borger ED. Structural basis of substrate recognition and catalysis by fucosyltransferase 8. J Biol Chem. 2020 May 8;295(19):6677-6688. doi: 10.1074/jbc.RA120.013291. Epub, 2020 Mar 27. PMID:32220931 doi:http://dx.doi.org/10.1074/jbc.RA120.013291
|
