Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
evolution
homoglutathione synthetase, EC 6.3.2.23, has evolved from glutathione synthetase by a single gene duplication event
evolution
Synechocystis glutathione synthase shares properties with other prokaryotic enzymes
evolution
Gsh2 belongs to the eu-GS superfamily
evolution
the enzyme encoded by GSH2 belongs to the eu-GC superfamily
evolution
the enzyme is a member of the ATP-grasp superfamily of enzymes
evolution
-
the enzyme is a member of the ATP-grasp superfamily of enzymes
-
malfunction
a gene disruptant mutant strain without GSH2 gene grows poorly because GSH2 encoes the second step in GSH synthesis, the dipeptide intermediate, gamma-glutamylcysteine, can partially substitute for GSH
malfunction
patients with genetic deficiencies in hGS suffer from a variety of symptoms, most notably hemolytic anemia and neurological disorders. Deficiencies of GSH are associated with a variety of diseases including Parkinson's disease, Alzheimer's disease, Lou Gehrig's disease, diabetes, cystic fibrosis, and HIV/AIDS. In the R221A mutant, the interchain salt bridge and hydrogen bonds between R221 and D24 are broken, and a new salt bridge forms between R34 and D24
malfunction
-
a gene disruptant mutant strain without GSH2 gene grows poorly because GSH2 encoes the second step in GSH synthesis, the dipeptide intermediate, gamma-glutamylcysteine, can partially substitute for GSH
-
metabolism
A485L/T486P mutant shows a shift the substrate specificity increased affinity of GSH2 for Ser as a substrate, while affinity to Gly is preserved. This provides a new biosynthetic pathway for hydroxymethyl glutathione, which is known to be synthesized from glutathione and Ser in a reaction catalysed by carboxypeptidase Y
metabolism
the bifunctional enzyme gshF catalyzes both steps of glutathione biosynthesis in Streptococcus thermophilus
metabolism
the enzyme catalyzes the second step of ATP-dependent glutathione biosynthesis from L-glutamate and L-cysteine
metabolism
the enzyme catalyzes the second step of ATP-dependent glutathione biosynthesis from L-glutamate and L-cysteine. GSH production occurs through two mechanisms: de novo synthesis and GSSG recycling. De novo synthesis occurs in a two-step reaction catalyzed by the two separate enzymes, glutamate cysteine ligase, EC 6.3.2.2, and glutathione synthetase
metabolism
-
the bifunctional enzyme gshF catalyzes both steps of glutathione biosynthesis in Streptococcus thermophilus
-
metabolism
-
the enzyme catalyzes the second step of ATP-dependent glutathione biosynthesis from L-glutamate and L-cysteine
-
metabolism
-
the enzyme catalyzes the second step of ATP-dependent glutathione biosynthesis from L-glutamate and L-cysteine. GSH production occurs through two mechanisms: de novo synthesis and GSSG recycling. De novo synthesis occurs in a two-step reaction catalyzed by the two separate enzymes, glutamate cysteine ligase, EC 6.3.2.2, and glutathione synthetase
-
physiological function
isolation of fully segregated gshB deletion mutants. The mutant strain lacks reduced glutathione but instead accumulates the precursor compound gamma-glutamylcysteine. The deletion strain grows slower than the wild-type strain under favorable conditions and exhibits extremely reduced growth or death when subjected to conditions promoting oxidative stress. After subjecting the strains to multiple environmental and redox perturbations, we found that conditions promoting growth stimulate glutathione biosynthesis. Cellular GSH and gamma-glutamylcysteine content decline following exposure to dark and blue light and during photoheterotrophic growth. A rapid depletion of GSH and gamma-glutamylcysteine is observed in the wild type and the mutant strain, when cells are starved for nitrate or sulfate
physiological function
glutathione biosynthesis catalysed by glutamate-cysteine ligase, EC 6.3.2.2, and glutathione synthetase is essential for maintaining redox homoeostasis and protection against oxidative damage in diverse eukaroytes and bacteria
physiological function
regulation of hGS plays a critical role in maintaining the cellular glutathione levels required to relieve oxidative stress
physiological function
the bifunctional GSH synthetase catalyzes two steps in GSH synthesis, which are usually catalyzed through L-glutamate L-cysteine ligase (gamma-GCS) and L-glutathione synthetase (GS)
physiological function
the enzyme is important in the biosynthesis of glutathione, the rate of GSH formation is limited by Gsh1 (EC 6.3.2.2), catalyzing the first step of the pathway
physiological function
the enzyme is required for biosynthesis of glutathione. Glutathione (GSH) fulfills a variety of metabolic functions, participates in oxidative stress response, and defends against toxic actions of heavy metals and xenobiotics
physiological function
-
the bifunctional GSH synthetase catalyzes two steps in GSH synthesis, which are usually catalyzed through L-glutamate L-cysteine ligase (gamma-GCS) and L-glutathione synthetase (GS)
-
physiological function
-
the enzyme is important in the biosynthesis of glutathione, the rate of GSH formation is limited by Gsh1 (EC 6.3.2.2), catalyzing the first step of the pathway
-
physiological function
-
the enzyme is required for biosynthesis of glutathione. Glutathione (GSH) fulfills a variety of metabolic functions, participates in oxidative stress response, and defends against toxic actions of heavy metals and xenobiotics
-
additional information
structure comparisons and homology structure molecular modelling of the GSH2 wild-type and mutant enzymes, overview
additional information
-
structure comparisons and homology structure molecular modelling of the GSH2 wild-type and mutant enzymes, overview
additional information
the active site is composed of three highly conserved catalytic loops, notably the alanine rich A-loop, Asp458 is important for cooperativity and active site structure, it impacts the allostery of the enzyme. Asp458 is important for loop closure and is a critical residue within the enzyme's A-loop. Enzyme structure-function modeling, molecular dynamics, overview
additional information
-
the active site is composed of three highly conserved catalytic loops, notably the alanine rich A-loop, Asp458 is important for cooperativity and active site structure, it impacts the allostery of the enzyme. Asp458 is important for loop closure and is a critical residue within the enzyme's A-loop. Enzyme structure-function modeling, molecular dynamics, overview
additional information
the obligate homodimer human glutathione synthetase (hGS) provides an ideal system for exploring the role of protein-protein interactions in the structural stability, activity and allostery of enzymes. The two subunits interact at a relatively small dimer interface dominated by electrostatic interactions between residues S42, R221, and D24, these residues are crucial to function of hGS. While the ionic hydrogen bonds and salt bridges between S42, R221, and D24 do not mediate allosteric communication in hGS, these interactions have a dramatic impact on the activity and structural stability of the enzyme, molecular dynamics simulations, overview. Since D24 participates in two significant interactions (a salt bridge with R221 and an ionic hydrogen bond with S42), this residue plays the largest role in hGS activity and stability. Structure and stability comparisons of wild-type enzyme and mutant enzymes, overview
additional information
-
the obligate homodimer human glutathione synthetase (hGS) provides an ideal system for exploring the role of protein-protein interactions in the structural stability, activity and allostery of enzymes. The two subunits interact at a relatively small dimer interface dominated by electrostatic interactions between residues S42, R221, and D24, these residues are crucial to function of hGS. While the ionic hydrogen bonds and salt bridges between S42, R221, and D24 do not mediate allosteric communication in hGS, these interactions have a dramatic impact on the activity and structural stability of the enzyme, molecular dynamics simulations, overview. Since D24 participates in two significant interactions (a salt bridge with R221 and an ionic hydrogen bond with S42), this residue plays the largest role in hGS activity and stability. Structure and stability comparisons of wild-type enzyme and mutant enzymes, overview