Structural highlights
DiseaseDCE1_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] FunctionDCE1_HUMAN Catalyzes the production of GABA. Publication Abstract from PubMedImbalances 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
| ||||||||||||||||||||
This page was last modified 22:50, 26 March 2025.