|3hbx, resolution 2.67Å ()|
|Gene:||At5g17330, GAD, GAD1, GDH1, MKP11.30, MKP11_18 (Arabidopsis thaliana)|
Crystal structure of GAD1 from Arabidopsis thaliana
Glutamate 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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[DCE1_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.
About this Structure
- Gut H, Dominici P, Pilati S, Astegno A, Petoukhov MV, Svergun DI, Grutter MG, Capitani G. A common structural basis for pH- and calmodulin-mediated regulation in plant glutamate decarboxylase. J Mol Biol. 2009 Sep 18;392(2):334-51. Epub 2009 Jul 4. PMID:19580813 doi:10.1016/j.jmb.2009.06.080