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| | <StructureSection load='5zic' size='340' side='right'caption='[[5zic]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='5zic' size='340' side='right'caption='[[5zic]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5zic]] is a 2 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=5ZIC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5ZIC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5zic]] is a 2 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=5ZIC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZIC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</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]] 2.1Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=Z4Y:'>Z4Y</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Z4Y:6-thio-alpha-D-mannopyranose'>Z4Y</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5zib|5zib]]</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=5zic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zic OCA], [https://pdbe.org/5zic PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zic RCSB], [https://www.ebi.ac.uk/pdbsum/5zic PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zic ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MGAT5, GGNT5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Alpha-1,6-mannosyl-glycoprotein_6-beta-N-acetylglucosaminyltransferase Alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.155 2.4.1.155] </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=5zic FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zic OCA], [http://pdbe.org/5zic PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zic RCSB], [http://www.ebi.ac.uk/pdbsum/5zic PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zic ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MGT5A_HUMAN MGT5A_HUMAN]] Catalyzes the addition of N-acetylglucosamine in beta 1-6 linkage to the alpha-linked mannose of biantennary N-linked oligosaccharides. It is one of the most important enzymes involved in the regulation of the biosynthesis of glycoprotein oligosaccharides. | + | [https://www.uniprot.org/uniprot/MGT5A_HUMAN MGT5A_HUMAN] Catalyzes the addition of N-acetylglucosamine in beta 1-6 linkage to the alpha-linked mannose of biantennary N-linked oligosaccharides. It is one of the most important enzymes involved in the regulation of the biosynthesis of glycoprotein oligosaccharides. |
| | <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: Alpha-1,6-mannosyl-glycoprotein 6-beta-N-acetylglucosaminyltransferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Nagae, M]] | + | [[Category: Nagae M]] |
| - | [[Category: Yamaguchi, Y]] | + | [[Category: Yamaguchi Y]] |
| - | [[Category: Glycosyltransferase cancer metastasis luminal protein]]
| + | |
| - | [[Category: Sugar binding protein]]
| + | |
| Structural highlights
Function
MGT5A_HUMAN Catalyzes the addition of N-acetylglucosamine in beta 1-6 linkage to the alpha-linked mannose of biantennary N-linked oligosaccharides. It is one of the most important enzymes involved in the regulation of the biosynthesis of glycoprotein oligosaccharides.
Publication Abstract from PubMed
N-acetylglucosaminyltransferase-V (GnT-V) alters the structure of specific N-glycans by modifying alpha1-6-linked mannose with a beta1-6-linked N-acetylglucosamine branch. beta1-6 branch formation on cell surface receptors accelerates cancer metastasis, making GnT-V a promising target for drug development. However, the molecular basis of GnT-V's catalytic mechanism and substrate specificity are not fully understood. Here, we report crystal structures of human GnT-V luminal domain with a substrate analog. GnT-V luminal domain is composed of a GT-B fold and two accessary domains. Interestingly, two aromatic rings sandwich the alpha1-6 branch of the acceptor N-glycan and restrain the global conformation, partly explaining the fine branch specificity of GnT-V. In addition, interaction of the substrate N-glycoprotein with GnT-V likely contributes to protein-selective and site-specific glycan modification. In summary, the acceptor-GnT-V complex structure suggests a catalytic mechanism, explains the previously observed inhibition of GnT-V by branching enzyme GnT-III, and provides a basis for the rational design of drugs targeting N-glycan branching.
Structure and mechanism of cancer-associated N-acetylglucosaminyltransferase-V.,Nagae M, Kizuka Y, Mihara E, Kitago Y, Hanashima S, Ito Y, Takagi J, Taniguchi N, Yamaguchi Y Nat Commun. 2018 Aug 23;9(1):3380. doi: 10.1038/s41467-018-05931-w. PMID:30140003[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nagae M, Kizuka Y, Mihara E, Kitago Y, Hanashima S, Ito Y, Takagi J, Taniguchi N, Yamaguchi Y. Structure and mechanism of cancer-associated N-acetylglucosaminyltransferase-V. Nat Commun. 2018 Aug 23;9(1):3380. doi: 10.1038/s41467-018-05931-w. PMID:30140003 doi:http://dx.doi.org/10.1038/s41467-018-05931-w
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