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| | <StructureSection load='6bw5' size='340' side='right'caption='[[6bw5]], [[Resolution|resolution]] 3.10Å' scene=''> | | <StructureSection load='6bw5' size='340' side='right'caption='[[6bw5]], [[Resolution|resolution]] 3.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bw5]] 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=6BW5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BW5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bw5]] 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=6BW5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BW5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PGW:(1R)-2-{[(S)-{[(2S)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(HEXADECANOYLOXY)METHYL]ETHYL+(9Z)-OCTADEC-9-ENOATE'>PGW</scene>, <scene name='pdbligand=TUM:TUNICAMYCIN'>TUM</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]] 3.1Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DPAGT1, DPAGT2 ([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=PGW:(1R)-2-{[(S)-{[(2S)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(HEXADECANOYLOXY)METHYL]ETHYL+(9Z)-OCTADEC-9-ENOATE'>PGW</scene>, <scene name='pdbligand=TUM:TUNICAMYCIN'>TUM</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-N-acetylglucosamine--dolichyl-phosphate_N-acetylglucosaminephosphotransferase UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.8.15 2.7.8.15] </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=6bw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bw5 OCA], [https://pdbe.org/6bw5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bw5 RCSB], [https://www.ebi.ac.uk/pdbsum/6bw5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bw5 ProSAT]</span></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=6bw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bw5 OCA], [http://pdbe.org/6bw5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bw5 RCSB], [http://www.ebi.ac.uk/pdbsum/6bw5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bw5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/GPT_HUMAN GPT_HUMAN]] DPAGT1-CDG;Congenital myasthenic syndromes with glycosylation defect. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/GPT_HUMAN GPT_HUMAN] DPAGT1-CDG;Congenital myasthenic syndromes with glycosylation defect. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GPT_HUMAN GPT_HUMAN]] Catalyzes the initial step in the synthesis of dolichol-P-P-oligosaccharides. | + | [https://www.uniprot.org/uniprot/GPT_HUMAN GPT_HUMAN] Catalyzes the initial step in the synthesis of dolichol-P-P-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: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase]]
| + | [[Category: Kuk ACY]] |
| - | [[Category: Kuk, A C.Y]] | + | [[Category: Lee S-Y]] |
| - | [[Category: Lee, S Y]] | + | [[Category: Mashalidis EH]] |
| - | [[Category: Mashalidis, E H]] | + | [[Category: Yoo J]] |
| - | [[Category: Yoo, J]] | + | |
| - | [[Category: Endoplasmic reticulum]]
| + | |
| - | [[Category: N-linked glycosylation]]
| + | |
| - | [[Category: Natural product]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transferase-antibiotic complex]]
| + | |
| - | [[Category: Tunicamycin]]
| + | |
| Structural highlights
Disease
GPT_HUMAN DPAGT1-CDG;Congenital myasthenic syndromes with glycosylation defect. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
GPT_HUMAN Catalyzes the initial step in the synthesis of dolichol-P-P-oligosaccharides.
Publication Abstract from PubMed
N-linked glycosylation is a predominant post-translational modification of protein in eukaryotes, and its dysregulation is the etiology of several human disorders. The enzyme UDP-N-acetylglucosamine:dolichyl-phosphate N-acetylglucosaminephosphotransferase (GlcNAc-1-P-transferase or GPT) catalyzes the first and committed step of N-linked glycosylation in the endoplasmic reticulum membrane, and it is the target of the natural product tunicamycin. Tunicamycin has potent antibacterial activity, inhibiting the bacterial cell wall synthesis enzyme MraY, but its usefulness as an antibiotic is limited by off-target inhibition of human GPT. Our understanding of how tunicamycin inhibits N-linked glycosylation and efforts to selectively target MraY are hampered by a lack of structural information. Here we present crystal structures of human GPT in complex with tunicamycin. Structural and functional analyses reveal the difference between GPT and MraY in their mechanisms of inhibition by tunicamycin. We demonstrate that this difference could be exploited to design MraY-specific inhibitors as potential antibiotics.
GlcNAc-1-P-transferase-tunicamycin complex structure reveals basis for inhibition of N-glycosylation.,Yoo J, Mashalidis EH, Kuk ACY, Yamamoto K, Kaeser B, Ichikawa S, Lee SY Nat Struct Mol Biol. 2018 Mar;25(3):217-224. doi: 10.1038/s41594-018-0031-y. Epub, 2018 Feb 19. PMID:29459785[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yoo J, Mashalidis EH, Kuk ACY, Yamamoto K, Kaeser B, Ichikawa S, Lee SY. GlcNAc-1-P-transferase-tunicamycin complex structure reveals basis for inhibition of N-glycosylation. Nat Struct Mol Biol. 2018 Mar;25(3):217-224. doi: 10.1038/s41594-018-0031-y. Epub, 2018 Feb 19. PMID:29459785 doi:http://dx.doi.org/10.1038/s41594-018-0031-y
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