Disease relevance of ECs3550

• Here, the cDNA for the heavy sub unit was expressed in Escherichia coli, and the recombinant enzyme was separated from E. coli gamma-glutamylcysteine synthetase and purified [1].
• The gene for gamma-glutamylcysteine synthetase from Thiobacillus ferrooxidans has low homology to its Escherichia coli equivalent and is linked to the gene for citrate synthase [2].
• Cloning, biochemical and phylogenetic characterizations of gamma-glutamylcysteine synthetase from Anabaena sp. PCC 7120 [3].

High impact information on ECs3550

• Crystal structure of gamma-glutamylcysteine synthetase: insights into the mechanism of catalysis by a key enzyme for glutathione homeostasis [4].
• Thus, resistance was abolished in the presence of buthionine sulfoximine, a selective inactivator of gamma-glutamylcysteine synthetase that decreases glutathione synthesis but that does not act directly to lower cellular glutathione levels [5].
• The nucleotide sequence of the gene for gamma-glutamylcysteine synthetase of Escherichia coli [6].
• We conclude that overexpression of gamma-ECS increases biosynthesis of glutathione and PCs, which in turn enhances Cd tolerance and accumulation [7].
• The gamma-ECS transgenic seedlings showed increased tolerance to Cd and had higher concentrations of PCs, gamma-GluCys, glutathione, and total non-protein thiols compared with wild-type (WT) seedlings [7].

Chemical compound and disease context of ECs3550

• To investigate rate-limiting factors for glutathione and phytochelatin (PC) production and the importance of these compounds for heavy metal tolerance, Indian mustard (Brassica juncea) was genetically engineered to overexpress the Escherichia coli gshI gene encoding gamma-glutamylcysteine synthetase (gamma-ECS), targeted to the plastids [7].
• ATP-dependent inactivation of Escherichia coli gamma-glutamylcysteine synthetase by L-glutamic acid gamma-monohydroxamate [8].
• Recognition of a cysteine substrate by E. coli gamma-glutamylcysteine synthetase probed by sulfoximine-based transition-state analogue inhibitors [9].
• A series of sulfoximine-based transition-state analogue inhibitors with a varying alkyl side chain was synthesized to probe the recognition of a Cys substrate by E. coli gamma-glutamylcysteine synthetase (gamma-GCS) [9].
• The enzymatic production of glutathione (GSH) has been studied in a bioreactor system using toluene-treated cells of Escherichia coli B transformed with recombinant plasmids for gamma-glutamylcysteine synthetase (GSH-I) and glutathione synthetase (GSH-II) [10].

Biological context of ECs3550

• The predicted sequence of the gamma-glutamylcysteine synthetase was found to have only 18% amino acid sequence identity to the equivalent enzyme from E. coli [2].
• The gene for gamma-glutamylcysteine synthetase (gshA) from Thiobacillus ferrooxidans was isolated from a family of cosmids by its ability to complement an Escherichia coli gshA trxA double mutant which was unable to grow on minimal medium lacking glutathione [2].

Anatomical context of ECs3550

• The hybrid poplar (Populus tremula x P. alba) was transformed to express the Escherichia coli gene for gamma-glutamylcysteine synthetase (EC 6.3.2.2: gamma-ECS) in the cytosol [11].

Associations of ECs3550 with chemical compounds

• Cadmium tolerance and accumulation in Indian mustard is enhanced by overexpressing gamma-glutamylcysteine synthetase [7].
• The lines strongly overexpressing gamma-ECS, ggs28, ggs11 and ggs5, contained enhanced foliar levels of cysteine (up to 2-fold), gamma-glutamylcysteine (5- to 20-fold) and glutathione (2- to 4-fold) [11].
• On the other hand, the maximum OERs for two GSH- mutants, 7 and 821, both deficient in gamma-glutamylcysteine synthetase, the penultimate enzyme in the GSH biosynthetic pathway, were about 2.7 and the K-values were about 0.06% O2 for both [12].
• Irreversible inhibition of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in the biosynthesis of glutathione (GSH), by L-buthionine-(S,R)-sulfoximine (BSO), induced the accumulation of ROS and augmented DeltapO(2) and LPS-mediated release of cytokines [13].

Analytical, diagnostic and therapeutic context of ECs3550

• Escherichia coli B gamma-glutamylcysteine synthetase: modification, purification, crystallization and preliminary crystallographic analysis [14].

References