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| | <StructureSection load='2zj4' size='340' side='right'caption='[[2zj4]], [[Resolution|resolution]] 2.20Å' scene=''> | | <StructureSection load='2zj4' size='340' side='right'caption='[[2zj4]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2zj4]] 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=2ZJ4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2ZJ4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2zj4]] 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=2ZJ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZJ4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGP:2-DEOXY-2-AMINO+GLUCITOL-6-PHOSPHATE'>AGP</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]] 2.2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zj3|2zj3]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGP:2-DEOXY-2-AMINO+GLUCITOL-6-PHOSPHATE'>AGP</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutamine--fructose-6-phosphate_transaminase_(isomerizing) Glutamine--fructose-6-phosphate transaminase (isomerizing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.16 2.6.1.16] </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=2zj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zj4 OCA], [https://pdbe.org/2zj4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zj4 RCSB], [https://www.ebi.ac.uk/pdbsum/2zj4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zj4 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=2zj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zj4 OCA], [http://pdbe.org/2zj4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zj4 RCSB], [http://www.ebi.ac.uk/pdbsum/2zj4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zj4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/GFPT1_HUMAN GFPT1_HUMAN]] Defects in GFPT1 are the cause of myasthenia, congenital, with tubular aggregates, type 1 (CMSTA1) [MIM:[http://omim.org/entry/610542 610542]]. A congenital myasthenic syndrome characterized by onset of proximal muscle weakness in the first decade. Individuals with this condition have a recognizable pattern of weakness of shoulder and pelvic girdle muscles, and sparing of ocular or facial muscles. EMG classically shows a decremental response to repeated nerve stimulation, a sign of neuromuscular junction dysfunction. Affected individuals show a favorable response to acetylcholinesterase (AChE) inhibitors.<ref>PMID:21310273</ref> | + | [https://www.uniprot.org/uniprot/GFPT1_HUMAN GFPT1_HUMAN] Defects in GFPT1 are the cause of myasthenia, congenital, with tubular aggregates, type 1 (CMSTA1) [MIM:[https://omim.org/entry/610542 610542]. A congenital myasthenic syndrome characterized by onset of proximal muscle weakness in the first decade. Individuals with this condition have a recognizable pattern of weakness of shoulder and pelvic girdle muscles, and sparing of ocular or facial muscles. EMG classically shows a decremental response to repeated nerve stimulation, a sign of neuromuscular junction dysfunction. Affected individuals show a favorable response to acetylcholinesterase (AChE) inhibitors.<ref>PMID:21310273</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GFPT1_HUMAN GFPT1_HUMAN]] Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins. | + | [https://www.uniprot.org/uniprot/GFPT1_HUMAN GFPT1_HUMAN] Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bando, M]] | + | [[Category: Bando M]] |
| - | [[Category: Kondo, K]] | + | [[Category: Kondo K]] |
| - | [[Category: Nakaishi, Y]] | + | [[Category: Nakaishi Y]] |
| - | [[Category: Tsuge, H]] | + | [[Category: Tsuge H]] |
| - | [[Category: Aldose/ketose isomerase]]
| + | |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Aminotransferase]]
| + | |
| - | [[Category: Glucosamine-6-phosphate synthase]]
| + | |
| - | [[Category: Glutamine amidotransferase]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Rossmann-like fold]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Disease
GFPT1_HUMAN Defects in GFPT1 are the cause of myasthenia, congenital, with tubular aggregates, type 1 (CMSTA1) [MIM:610542. A congenital myasthenic syndrome characterized by onset of proximal muscle weakness in the first decade. Individuals with this condition have a recognizable pattern of weakness of shoulder and pelvic girdle muscles, and sparing of ocular or facial muscles. EMG classically shows a decremental response to repeated nerve stimulation, a sign of neuromuscular junction dysfunction. Affected individuals show a favorable response to acetylcholinesterase (AChE) inhibitors.[1]
Function
GFPT1_HUMAN Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Glutamine:fructose-6-phosphate amidotransferase (GFAT) is a rate-limiting enzyme in the hexoamine biosynthetic pathway and plays an important role in type 2 diabetes. We now report the first structures of the isomerase domain of the human GFAT in the presence of cyclic glucose-6-phosphate and linear glucosamine-6-phosphate. The C-terminal tail including the active site displays a rigid conformation, similar to the corresponding Escherichia coli enzyme. The diversity of the CF helix near the active site suggests the helix is a major target for drug design. Our study provides insights into the development of therapeutic drugs for type 2 diabetes.
Structural analysis of human glutamine:fructose-6-phosphate amidotransferase, a key regulator in type 2 diabetes.,Nakaishi Y, Bando M, Shimizu H, Watanabe K, Goto F, Tsuge H, Kondo K, Komatsu M FEBS Lett. 2009 Jan 5;583(1):163-7. Epub 2008 Dec 6. PMID:19059404[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Senderek J, Muller JS, Dusl M, Strom TM, Guergueltcheva V, Diepolder I, Laval SH, Maxwell S, Cossins J, Krause S, Muelas N, Vilchez JJ, Colomer J, Mallebrera CJ, Nascimento A, Nafissi S, Kariminejad A, Nilipour Y, Bozorgmehr B, Najmabadi H, Rodolico C, Sieb JP, Steinlein OK, Schlotter B, Schoser B, Kirschner J, Herrmann R, Voit T, Oldfors A, Lindbergh C, Urtizberea A, von der Hagen M, Hubner A, Palace J, Bushby K, Straub V, Beeson D, Abicht A, Lochmuller H. Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect. Am J Hum Genet. 2011 Feb 11;88(2):162-72. doi: 10.1016/j.ajhg.2011.01.008. PMID:21310273 doi:10.1016/j.ajhg.2011.01.008
- ↑ Nakaishi Y, Bando M, Shimizu H, Watanabe K, Goto F, Tsuge H, Kondo K, Komatsu M. Structural analysis of human glutamine:fructose-6-phosphate amidotransferase, a key regulator in type 2 diabetes. FEBS Lett. 2009 Jan 5;583(1):163-7. Epub 2008 Dec 6. PMID:19059404 doi:http://dx.doi.org/S0014-5793(08)00953-8
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