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| | <StructureSection load='5lev' size='340' side='right'caption='[[5lev]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='5lev' size='340' side='right'caption='[[5lev]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5lev]] is a 1 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=5LEV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LEV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5lev]] 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=5LEV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LEV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</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='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=UNL:UNKNOWN+LIGAND'>UNL</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=5lev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lev OCA], [https://pdbe.org/5lev PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lev RCSB], [https://www.ebi.ac.uk/pdbsum/5lev PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lev 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=5lev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lev OCA], [http://pdbe.org/5lev PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lev RCSB], [http://www.ebi.ac.uk/pdbsum/5lev PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lev 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: Arrowsmith CH]] |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Beeson D]] |
| - | [[Category: Beeson, D]] | + | [[Category: Belaya K]] |
| - | [[Category: Belaya, K]] | + | [[Category: Berridge G]] |
| - | [[Category: Berridge, G]] | + | [[Category: Bountra C]] |
| - | [[Category: Bountra, C]] | + | [[Category: Burgess-Brown N]] |
| - | [[Category: Burgess-Brown, N]] | + | [[Category: Carpenter EP]] |
| - | [[Category: Carpenter, E P]] | + | [[Category: Chalk R]] |
| - | [[Category: Chalk, R]] | + | [[Category: Chu A]] |
| - | [[Category: Chu, A]] | + | [[Category: Dong L]] |
| - | [[Category: Dong, L]] | + | [[Category: Dong YY]] |
| - | [[Category: Dong, Y Y]] | + | [[Category: Edwards AM]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Goubin S]] |
| - | [[Category: Goubin, S]] | + | [[Category: Kupinska K]] |
| - | [[Category: Kupinska, K]] | + | [[Category: Mahajan P]] |
| - | [[Category: Mahajan, P]] | + | [[Category: Mukhopadhyay S]] |
| - | [[Category: Mukhopadhyay, S]] | + | [[Category: Pike ACW]] |
| - | [[Category: Pike, A C.W]] | + | [[Category: Tessitore A]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Wang D]] |
| - | [[Category: Tessitore, A]] | + | |
| - | [[Category: Wang, D]] | + | |
| - | [[Category: Congenital myasthenic syndrome 13]]
| + | |
| - | [[Category: Integral membrane protein]]
| + | |
| - | [[Category: Protein glycosylation]]
| + | |
| - | [[Category: Sgc]]
| + | |
| - | [[Category: Transferase]]
| + | |
| 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
Protein N-glycosylation is a widespread post-translational modification. The first committed step in this process is catalysed by dolichyl-phosphate N-acetylglucosamine-phosphotransferase DPAGT1 (GPT/E.C. 2.7.8.15). Missense DPAGT1 variants cause congenital myasthenic syndrome and disorders of glycosylation. In addition, naturally-occurring bactericidal nucleoside analogues such as tunicamycin are toxic to eukaryotes due to DPAGT1 inhibition, preventing their clinical use. Our structures of DPAGT1 with the substrate UDP-GlcNAc and tunicamycin reveal substrate binding modes, suggest a mechanism of catalysis, provide an understanding of how mutations modulate activity (thus causing disease) and allow design of non-toxic "lipid-altered" tunicamycins. The structure-tuned activity of these analogues against several bacterial targets allowed the design of potent antibiotics for Mycobacterium tuberculosis, enabling treatment in vitro, in cellulo and in vivo, providing a promising new class of antimicrobial drug.
Structures of DPAGT1 Explain Glycosylation Disease Mechanisms and Advance TB Antibiotic Design.,Dong YY, Wang H, Pike ACW, Cochrane SA, Hamedzadeh S, Wyszynski FJ, Bushell SR, Royer SF, Widdick DA, Sajid A, Boshoff HI, Park Y, Lucas R, Liu WM, Lee SS, Machida T, Minall L, Mehmood S, Belaya K, Liu WW, Chu A, Shrestha L, Mukhopadhyay SMM, Strain-Damerell C, Chalk R, Burgess-Brown NA, Bibb MJ, Barry Iii CE, Robinson CV, Beeson D, Davis BG, Carpenter EP Cell. 2018 Nov 1;175(4):1045-1058.e16. doi: 10.1016/j.cell.2018.10.037. PMID:30388443[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dong YY, Wang H, Pike ACW, Cochrane SA, Hamedzadeh S, Wyszynski FJ, Bushell SR, Royer SF, Widdick DA, Sajid A, Boshoff HI, Park Y, Lucas R, Liu WM, Lee SS, Machida T, Minall L, Mehmood S, Belaya K, Liu WW, Chu A, Shrestha L, Mukhopadhyay SMM, Strain-Damerell C, Chalk R, Burgess-Brown NA, Bibb MJ, Barry Iii CE, Robinson CV, Beeson D, Davis BG, Carpenter EP. Structures of DPAGT1 Explain Glycosylation Disease Mechanisms and Advance TB Antibiotic Design. Cell. 2018 Nov 1;175(4):1045-1058.e16. doi: 10.1016/j.cell.2018.10.037. PMID:30388443 doi:http://dx.doi.org/10.1016/j.cell.2018.10.037
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