3vp6

From Proteopedia

(Difference between revisions)

Current revision

Structural characterization of Glutamic Acid Decarboxylase; insights into the mechanism of autoinactivation

Structural highlights

3vp6 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

Publication Abstract from PubMed

Imbalances in GABA homeostasis underlie psychiatric and movement disorders. The ability of the 65kDa isoform of glutamic acid decarboxylase, GAD65, to control synaptic GABA levels is influenced through its capacity to auto-inactivate. In contrast, the GAD67 isoform is constitutively active. Previous structural insights suggest that flexibility in the GAD65 catalytic loop drives enzyme inactivation. To test this idea, we constructed a panel of GAD65/67 chimeras and compared the ability of these molecules to auto-inactivate. Together, our data reveal the important finding that the C-terminal domain of GAD plays a key role in controlling GAD65 auto-inactivation. In support of these findings, we determined the X-ray crystal structure of a GAD65/67 chimera that reveals the conformation of the catalytic loop is intimately linked to the C-terminal domain.

Structural characterization on the mechanism of auto-inactivation for Human Glutamic Acid Decarboxylase.,Langendorf CG, Tuck KL, Key TL, Fenalti G, Pike RN, Rosado CJ, Wong AS, Buckle AM, Law RH, Whisstock JC Biosci Rep. 2012 Nov 5. PMID:23126365^[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
↑ Langendorf CG, Tuck KL, Key TL, Fenalti G, Pike RN, Rosado CJ, Wong AS, Buckle AM, Law RH, Whisstock JC. Structural characterization on the mechanism of auto-inactivation for Human Glutamic Acid Decarboxylase. Biosci Rep. 2012 Nov 5. PMID:23126365 doi:10.1042/BSR20120111

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3vp6"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 3vp6 is ON HOLD
+==Structural characterization of Glutamic Acid Decarboxylase; insights into the mechanism of autoinactivation==
+<StructureSection load='3vp6' size='340' side='right'caption='[[3vp6]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3vp6]] 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=3VP6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VP6 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HLD:4-OXO-4H-PYRAN-2,6-DICARBOXYLIC+ACID'>HLD</scene>, <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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3vp6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vp6 OCA], [https://pdbe.org/3vp6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vp6 RCSB], [https://www.ebi.ac.uk/pdbsum/3vp6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vp6 ProSAT]</span></td></tr>
+</table>
+== 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>
+== Function ==
+[https://www.uniprot.org/uniprot/DCE1_HUMAN DCE1_HUMAN] Catalyzes the production of GABA.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Imbalances in GABA homeostasis underlie psychiatric and movement disorders. The ability of the 65kDa isoform of glutamic acid decarboxylase, GAD65, to control synaptic GABA levels is influenced through its capacity to auto-inactivate. In contrast, the GAD67 isoform is constitutively active. Previous structural insights suggest that flexibility in the GAD65 catalytic loop drives enzyme inactivation. To test this idea, we constructed a panel of GAD65/67 chimeras and compared the ability of these molecules to auto-inactivate. Together, our data reveal the important finding that the C-terminal domain of GAD plays a key role in controlling GAD65 auto-inactivation. In support of these findings, we determined the X-ray crystal structure of a GAD65/67 chimera that reveals the conformation of the catalytic loop is intimately linked to the C-terminal domain.
-Authors: Langendorf, C.G., Tuck, K.L., Key, T.L.G., Rosado, C.J., Wong, A.S.M., Fenalti, G., Buckle, A.M., Law, R.H.P., Whisstock, J.C.
+Structural characterization on the mechanism of auto-inactivation for Human Glutamic Acid Decarboxylase.,Langendorf CG, Tuck KL, Key TL, Fenalti G, Pike RN, Rosado CJ, Wong AS, Buckle AM, Law RH, Whisstock JC Biosci Rep. 2012 Nov 5. PMID:23126365<ref>PMID:23126365</ref>
-Description: Structural characterization of Glutamic Acid Decarboxylase; insights into the mechanism of autoinactivation
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3vp6" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Buckle AM]]
+[[Category: Fenalti G]]
+[[Category: Key TLG]]
+[[Category: Langendorf CG]]
+[[Category: Law RHP]]
+[[Category: Rosado CJ]]
+[[Category: Tuck KL]]
+[[Category: Whisstock JC]]
+[[Category: Wong ASM]]

3vp6

From Proteopedia

Current revision

Structural characterization of Glutamic Acid Decarboxylase; insights into the mechanism of autoinactivation

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox