2GWC

Crystal structure of plant glutamate cysteine ligase in complex with a transition state analogue

Summary for 2GWC

• Entry DOI: 10.2210/pdb2gwc/pdb
• Descriptor: Glutamate cysteine ligase, MAGNESIUM ION, (2S)-2-amino-4-(S-butylsulfonimidoyl)butanoic acid, ... (4 entities in total)
• Functional Keywords: disulfide bridges, glutathione biosynthesis, beta-hairpin, redox regulation, ligase
• Biological source: Brassica juncea
• Total number of polymer chains: 8
• Total formula weight: 416519.13

Authors

Hothorn, M.,Wachter, A.,Gromes, R.,Stuwe, T.,Rausch, T.,Scheffzek, K. (deposition date: 2006-05-04, release date: 2006-06-20, Last modification date: 2024-10-30)

Primary citation

Hothorn, M.,Wachter, A.,Gromes, R.,Stuwe, T.,Rausch, T.,Scheffzek, K.
Structural basis for the redox control of plant glutamate cysteine ligase.
J.Biol.Chem., 281:27557-27565, 2006

PubMed Abstract: Glutathione (GSH) plays a crucial role in plant metabolism and stress response. The rate-limiting step in the biosynthesis of GSH is catalyzed by glutamate cysteine ligase (GCL) the activity of which is tightly regulated. The regulation of plant GCLs is poorly understood. The crystal structure of substrate-bound GCL from Brassica juncea at 2.1-A resolution reveals a plant-unique regulatory mechanism based on two intramolecular redox-sensitive disulfide bonds. Reduction of one disulfide bond allows a beta-hairpin motif to shield the active site of B. juncea GCL, thereby preventing the access of substrates. Reduction of the second disulfide bond reversibly controls dimer to monomer transition of B. juncea GCL that is associated with a significant inactivation of the enzyme. These regulatory events provide a molecular link between high GSH levels in the plant cell and associated down-regulation of its biosynthesis. Furthermore, known mutations in the Arabidopsis GCL gene affect residues in the close proximity of the active site and thus explain the decreased GSH levels in mutant plants. In particular, the mutation in rax1-1 plants causes impaired binding of cysteine.

PubMed: 16766527
DOI: 10.1074/jbc.M602770200

Experimental method

X-RAY DIFFRACTION (2.18 Å)