3hbx | pdb_00003hbx
Crystal structure of GAD1 from Arabidopsis thaliana
Structural highlights
FunctionDCE1_ARATH Catalyzes the production of GABA. The calmodulin-binding is calcium-dependent and it is proposed that this may, directly or indirectly, form a calcium regulated control of GABA biosynthesis.[1] 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 PubMedGlutamate decarboxylase (Gad) catalyzes glutamate to gamma-aminobutyrate conversion. Plant Gad is a approximately 340 kDa hexamer, involved in development and stress response, and regulated by pH and binding of Ca(2+)/calmodulin (CaM) to the C-terminal domain. We determined the crystal structure of Arabidopsis thaliana Gad1 in its CaM-free state, obtained a low-resolution structure of the calmodulin-activated Gad complex by small-angle X-ray scattering and identified the crucial residues, in the C-terminal domain, for regulation by pH and CaM binding. CaM activates Gad1 in a unique way by relieving two C-terminal autoinhibition domains of adjacent active sites, forming a 393 kDa Gad1-CaM complex with an unusual 1:3 stoichiometry. The complex is loosely packed: thanks to the flexible linkers connecting the enzyme core with the six C-terminal regulatory domains, the CaM molecules retain considerable positional and orientational freedom with respect to Gad1. The complex thus represents a prototype for a novel CaM-target interaction mode. Thanks to its two levels of regulation, both targeting the C-terminal domain, Gad can respond flexibly to different kinds of cellular stress occurring at different pH values. A common structural basis for pH- and calmodulin-mediated regulation in plant glutamate decarboxylase.,Gut H, Dominici P, Pilati S, Astegno A, Petoukhov MV, Svergun DI, Grutter MG, Capitani G J Mol Biol. 2009 Sep 18;392(2):334-51. Epub 2009 Jul 4. PMID:19580813[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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