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| | <StructureSection load='2okj' size='340' side='right'caption='[[2okj]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='2okj' size='340' side='right'caption='[[2okj]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2okj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OKJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2okj]] 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=2OKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OKJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABU:GAMMA-AMINO-BUTANOIC+ACID'>ABU</scene>, <scene name='pdbligand=PLZ:4-[({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)AMINO]BUTANOIC+ACID'>PLZ</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]] 2.3Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABU:GAMMA-AMINO-BUTANOIC+ACID'>ABU</scene>, <scene name='pdbligand=LLP:(2S)-2-AMINO-6-[[3-HYDROXY-2-METHYL-5-(PHOSPHONOOXYMETHYL)PYRIDIN-4-YL]METHYLIDENEAMINO]HEXANOIC+ACID'>LLP</scene>, <scene name='pdbligand=PLZ:4-[({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)AMINO]BUTANOIC+ACID'>PLZ</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2okk|2okk]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GAD1, GAD, GAD67 ([https://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'>[https://en.wikipedia.org/wiki/Glutamate_decarboxylase Glutamate decarboxylase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.15 4.1.1.15] </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=2okj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2okj OCA], [https://pdbe.org/2okj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2okj RCSB], [https://www.ebi.ac.uk/pdbsum/2okj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2okj ProSAT]</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=2okj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2okj OCA], [https://pdbe.org/2okj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2okj RCSB], [https://www.ebi.ac.uk/pdbsum/2okj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2okj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/DCE1_HUMAN DCE1_HUMAN]] Defects in GAD1 are the cause of cerebral palsy spastic quadriplegic type 1 (CPSQ1) [MIM:[https://omim.org/entry/603513 603513]]. A non-progressive disorder of movement and/or posture resulting from defects in the developing central nervous system. Affected individuals manifest symmetrical, non-progressive spasticity and no adverse perinatal history or obvious underlying alternative diagnosis. Developmental delay, mental retardation and sometimes epilepsy can be part of the clinical picture.<ref>PMID:15571623</ref>
| + | [https://www.uniprot.org/uniprot/DCE1_HUMAN DCE1_HUMAN] Defects in GAD1 are the cause of cerebral palsy spastic quadriplegic type 1 (CPSQ1) [MIM:[https://omim.org/entry/603513 603513]. A non-progressive disorder of movement and/or posture resulting from defects in the developing central nervous system. Affected individuals manifest symmetrical, non-progressive spasticity and no adverse perinatal history or obvious underlying alternative diagnosis. Developmental delay, mental retardation and sometimes epilepsy can be part of the clinical picture.<ref>PMID:15571623</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DCE1_HUMAN DCE1_HUMAN]] Catalyzes the production of GABA.
| + | [https://www.uniprot.org/uniprot/DCE1_HUMAN DCE1_HUMAN] Catalyzes the production of GABA. |
| | == 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: Glutamate decarboxylase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Buckle, A M]] | + | [[Category: Buckle AM]] |
| - | [[Category: Fenalti, G]] | + | [[Category: Fenalti G]] |
| - | [[Category: Law, R H.P]] | + | [[Category: Law RHP]] |
| - | [[Category: Whisstock, J C]] | + | [[Category: Whisstock JC]] |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Plp-dependent decarboxylase]]
| + | |
| Structural highlights
Disease
DCE1_HUMAN Defects in GAD1 are the cause of cerebral palsy spastic quadriplegic type 1 (CPSQ1) [MIM:603513. A non-progressive disorder of movement and/or posture resulting from defects in the developing central nervous system. Affected individuals manifest symmetrical, non-progressive spasticity and no adverse perinatal history or obvious underlying alternative diagnosis. Developmental delay, mental retardation and sometimes epilepsy can be part of the clinical picture.[1]
Function
DCE1_HUMAN Catalyzes the production of GABA.
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
Gamma-aminobutyric acid (GABA) is synthesized by two isoforms of the pyridoxal 5'-phosphate-dependent enzyme glutamic acid decarboxylase (GAD65 and GAD67). GAD67 is constitutively active and is responsible for basal GABA production. In contrast, GAD65, an autoantigen in type I diabetes, is transiently activated in response to the demand for extra GABA in neurotransmission, and cycles between an active holo form and an inactive apo form. We have determined the crystal structures of N-terminal truncations of both GAD isoforms. The structure of GAD67 shows a tethered loop covering the active site, providing a catalytic environment that sustains GABA production. In contrast, the same catalytic loop is inherently mobile in GAD65. Kinetic studies suggest that mobility in the catalytic loop promotes a side reaction that results in cofactor release and GAD65 autoinactivation. These data reveal the molecular basis for regulation of GABA homeostasis.
GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop.,Fenalti G, Law RH, Buckle AM, Langendorf C, Tuck K, Rosado CJ, Faux NG, Mahmood K, Hampe CS, Banga JP, Wilce M, Schmidberger J, Rossjohn J, El-Kabbani O, Pike RN, Smith AI, Mackay IR, Rowley MJ, Whisstock JC Nat Struct Mol Biol. 2007 Apr;14(4):280-6. Epub 2007 Mar 25. PMID:17384644[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lynex CN, Carr IM, Leek JP, Achuthan R, Mitchell S, Maher ER, Woods CG, Bonthon DT, Markham AF. Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders. BMC Neurol. 2004 Nov 30;4(1):20. PMID:15571623 doi:10.1186/1471-2377-4-20
- ↑ Fenalti G, Law RH, Buckle AM, Langendorf C, Tuck K, Rosado CJ, Faux NG, Mahmood K, Hampe CS, Banga JP, Wilce M, Schmidberger J, Rossjohn J, El-Kabbani O, Pike RN, Smith AI, Mackay IR, Rowley MJ, Whisstock JC. GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop. Nat Struct Mol Biol. 2007 Apr;14(4):280-6. Epub 2007 Mar 25. PMID:17384644 doi:10.1038/nsmb1228
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