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Mary E. Anderson - One of the best experts on this subject based on the ideXlab platform.
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The Role of Strong Electrostatic Interactions at the Dimer Interface of Human Glutathione Synthetase
The Protein Journal, 2014Co-Authors: Margarita C. Jesus, Thomas R. Cundari, Kerri D. Slavens, Khaldoon A. Barakat, Brandall L. Ingle, Bisesh Shrestha, Mary E. AndersonAbstract: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 active sites of hGS, which are 40 Å apart, display allosteric modulation by the substrate γ-glutamylcysteine (γ-GC) during the synthesis of Glutathione, a key cellular antioxidant. The two subunits interact at a relatively small dimer interface dominated by electrostatic interactions between S42, R221, and D24. Alanine scans of these sites result in enzymes with decreased activity, altered γ-GC affinity, and decreased thermal stability. Molecular dynamics simulations indicate these mutations disrupt interchain bonding and impact the tertiary structure 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.
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Valine 44 and valine 45 of human Glutathione Synthetase are key for subunit stability and negative cooperativity.
Biochemical and biophysical research communications, 2011Co-Authors: Kerri D. Slavens, Thomas R. Cundari, Teresa R. Brown, Khaldoon A. Barakat, Mary E. AndersonAbstract:It was hypothesized that residues Val44 and Val45 serve as important residues for human Glutathione Synthetase (hGS) function and stability given their location at the dimer interface of this enzyme. Computational studies suggest that mutation at Val45 has more impact on the structure and stability of hGS than does mutation at Val44. Experimentally, enzymes with mutations at the 44 and or 45 positions of hGS were prepared, purified and assayed for initial activity. Val45 position mutations (either to alanine or tryptophan) have a greater impact on enzyme activity than do mutations at Val44. Differential scanning calorimetry experiments reveal a loss of stability in all mutant enzymes, with V45 mutations being less stable than the corresponding Val44 mutations. The γ-GluABA substrate affinity remains unaltered in V44A and V45A mutant enzymes, but increases when tryptophan is introduced at either of these positions. Hill coefficients trend towards less negative cooperativity with the exception of V45W mutant hGS. These results imply that residues V44 and V45 are located along the allosteric pathway of this negatively cooperative dimeric enzyme, that their mutation impacts the allosteric pathway more than it does the active site of hGS, and that these residues (and by extension the dimer interface in which they are located) are integral to the stability of human Glutathione Synthetase.
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the role of the glycine triad in human Glutathione Synthetase
Biochemical and Biophysical Research Communications, 2010Co-Authors: Adriana Dinescu, Thomas R. Cundari, Teresa R. Brown, Sarah Barelier, Mary E. AndersonAbstract:Experimental kinetics and computational modeling of human Glutathione Synthetase (hGS) support the significant role of the G-loop glycine triad (G369, G370, G371) for activity of this ATP-grasp enzyme. Enzyme kinetic experiments indicate that G369V and G370V mutant hGS have little activity (<0.7 and 0.3%, respectively, versus wild-type hGS). However, G371V retains ∼13% of the activity of wild-type hGS. With respect to G-loop:A-loop interaction in hGS, mutations at Gly369 and Gly370 decrease ligand binding and prevent active site closure and protection. This research indicates that Gly369 and Gly370 have essential roles in hGS, while Gly371 has a lesser involvement. Implications for glycine-rich ensembles in other phosphate-binding enzymes are discussed.
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The role of the glycine triad in human Glutathione Synthetase
Biochemical and biophysical research communications, 2010Co-Authors: Adriana Dinescu, Thomas R. Cundari, Teresa R. Brown, Sarah Barelier, Mary E. AndersonAbstract:Experimental kinetics and computational modeling of human Glutathione Synthetase (hGS) support the significant role of the G-loop glycine triad (G369, G370, G371) for activity of this ATP-grasp enzyme. Enzyme kinetic experiments indicate that G369V and G370V mutant hGS have little activity (
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catalytic loop motion in human Glutathione Synthetase a molecular modeling approach
Biochemical and Biophysical Research Communications, 2007Co-Authors: Adriana Dinescu, Mary E. Anderson, Thomas R. CundariAbstract:Conformational changes of three flexible loops (G, A, and S) in human Glutathione Synthetase (hGS) arise to accommodate the substrates inside the active site. The crystal structure of hGS, a member of the ATP-grasp superfamily, has been reported only for the product-enzyme complex. To study the function of the hGS loops, molecular dynamics simulations are performed on three different conformational models: unbound enzyme, reactant-enzyme, and product-enzyme complex of hGS. The conformational changes among the three models are analyzed and the roles of the loops during the catalytic process are described. The modeled structures of hGS show that the central portions of the G- and A-loop have a double role in the reactant complex conformation: they bind the substrates and simultaneously interact with each other through an extensive network of hydrogen bonds. The present study proposes that these favorable loop-ligand and loop-loop interactions are required for opening and closing of the active site of hGS. Additionally, this research identifies important amino acid residues and explains their function within the catalytic loops of hGS.
Agne Larsson - One of the best experts on this subject based on the ideXlab platform.
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Rod-cone dystrophy with maculopathy in genetic Glutathione Synthetase deficiency: a morphologic and electrophysiologic study.
Ophthalmology, 2008Co-Authors: Marie Burstedt, Agne Larsson, Ellinor Ristoff, Lillemor WachtmeisterAbstract:PURPOSE: To describe the retinal findings in 2 young adults with Glutathione Synthetase (GS) deficiency, an autosomal-recessive inborn error of Glutathione (GSH) metabolism. DESIGN: Report of 2 cas ...
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Progressive retinal dystrophy in two sisters with Glutathione Synthetase (GS) deficiency.
Journal of inherited metabolic disease, 2007Co-Authors: Ellinor Ristoff, Agne Larsson, Marie Burstedt, Lillemor WachtmeisterAbstract:We report the ophthalmological findings of two sisters with severe Glutathione Synthetase deficiency, an autosomal recessive inborn error of metabolism resulting in very low intracellular levels of the free-radical scavenger Glutathione. The patients were investigated because of declining visual acuity. The most prominent finding was progressive retinal dystrophy with hyperpigmentations and maculopathy. Generally disturbed functioning of both the outer and inner layers of the retina resulted in attenuated or nearly abolished electroretinograms. These findings agree with a rod/cone type of retinal dystrophy, and we suggest that this is due to Glutathione deficiency. Treatment with antioxidants such as vitamins E and C seems to prevent the progression of CNS damage. We speculate that it might also prevent retinal dystrophy in patients with Glutathione Synthetase deficiency. We suggest that patients with retinal dystrophy and additional neurological signs should be investigated for a defect in Glutathione metabolism. Also, we recommend that patients with low levels of Glutathione should be examined for retinal dystrophy. Our results suggest that a decreased capacity for scavenging reactive oxygen species and/or increased oxidative stress may cause retinal dystrophy. If this is the case, the redox state in the retina should be a potentially useful therapeutic target to prevent reduced visual function and blindness.
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Human hereditary Glutathione Synthetase deficiency: kinetic properties of mutant enzymes.
The Biochemical journal, 2004Co-Authors: Runa Njålsson, Katarina Carlsson, Vikas Bhansali, Lennart Nilsson, Rudolf Ladenstein, Mary Anderson, Agne Larsson, Svante NorgrenAbstract:Patients with hereditary Glutathione Synthetase deficiency suffer from haemolytic anaemia, 5-oxoprolinuria, metabolic acidosis, recurrent bacterial infections and various degrees of central nervous system dysfunction. To investigate the molecular basis of the mutations associated with this disease, seven naturally occurring missense mutations [L188P (Leu188-->Pro), D219A, D219G, Y270C, Y270H, R283C and P314L] were expressed using a His-tagged, Escherichia coli-based expression system. Effects of the mutations on kinetic properties, including negative co-operative binding of gamma-glutamyl substrate, were evaluated. The mutation P314L did not have any major effect on these parameters and was classified as a neutral mutation. The remaining mutations decreased V(max) to 2-27% of wild-type activity. Negative co-operativity for gamma-gluABA (L-gamma-glutamyl-L-alpha-aminobutyric acid) was abolished in five mutant recombinant enzymes, whereas for one mutant enzyme, this co-operativity changed from negative to positive. The structural consequences of the mutations were interpreted on the basis of the known structure of the wild-type enzyme.
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Glutathione Synthetase deficiency associated with antenatal cerebral bleeding.
Journal of inherited metabolic disease, 2004Co-Authors: L. W. Brüggemann, Agne Larsson, Floris Groenendaal, E. Ristoff, Marinus Duran, J. A. C. Van Lier, Lambertus Dorland, Ruud Berger, T. J. De KoningAbstract:We present a newborn with Glutathione Synthetase deficiency and intracranial haemorrhages. Because the latter are rare in term newborns a possible relationship with Glutathione Synthetase deficiency will be discussed.
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Diagnostics in patients with Glutathione Synthetase deficiency but without mutations in the exons of the GSS gene.
Human mutation, 2003Co-Authors: Runa Njålsson, Katarina Carlsson, Agne Larsson, Andreas Winkler, Svante NorgrenAbstract:The synthesis of the ubiquitous tripeptide Glutathione is impaired in patients with Glutathione Synthetase deficiency. The defect is inherited in an autosomal recessive manner, and the diagnosis is based on clinical, biochemical, and genetic criteria. In seven of our 30 index cases, however, no disease causing mutations could be identified in the coding exons or exon-intron boundaries of the Glutathione Synthetase gene GSS. These patients had severely decreased Glutathione Synthetase activities in lysates of cultured fibroblasts, and the levels of the enzyme were undetectable using a polyclonal antibody raised against human Glutathione Synthetase. RT-PCR mediated sequence analysis revealed previously not reported splice mutations in all patients. Thus, we conclude that in the investigation of patients with Glutathione Synthetase deficiency, and probably other genetic diseases as well, it might be time saving to initiate mutation analysis with sequencing of mRNA.
David J Oliver - One of the best experts on this subject based on the ideXlab platform.
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Glutathione Synthetase: similarities of the proteins from Schizosaccharomyces pombe and Arabidopsis thaliana.
Biochemical Journal, 1997Co-Authors: Chang-lin Wang, David J OliverAbstract:Glutathione Synthetase predicted from the reported gene sequence from Schizosaccharomyces pombe is substantially smaller than the equivalent protein predicted from the cDNAs sequenced from Arabidopsis thaliana, Saccharomyces cerevisiae and other eukaryotes. Sequence alignments of the proteins encoded by the cDNA clones for Glutathione Synthetase from Arabidopsis and S. pombe show that the Arabidopsis protein contains 200 extra amino acids at the N-terminus. In order to test if this sequence is essential in the function of the protein, the full-length Arabidopsis protein and as two N-terminal deletions (Delta67-71 and Delta67-200) were expressed in S. pombe mutant MN101, which lacks endogenous Glutathione Synthetase activity. Although the wild-type plant cDNA could complement the yeast mutation, neither deletion mutant was able to restore Glutathione-dependent cadmium resistance. When the three proteins were expressed as fusion proteins in Escherichia coli, they accumulated to the same level, but only the plasmid containing the full-length cDNA, pFLAG222, produced detectable enzyme activity in vitro. These results suggested that the N-terminus of the Arabidopsis Glutathione Synthetase is essential for its function and opened up the possibility that there was a sequencing error in the reported S. pombe sequence. Therefore the gsh2 sequence from wild-type S. pombe and the mutant strain MN101 were determined. The wild-type S. pombe gsh2 encodes a protein that is about the same length as that found in Arabidopsis, and the MN101 mutation involves a frameshift mutation early in the Glutathione Synthetase reading frame.
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Identification of a putative flexible loop in Arabidopsis Glutathione Synthetase.
Biochemical Journal, 1997Co-Authors: Chang-lin Wang, David J OliverAbstract:Glutathione Synthetase catalyses the ATP-dependent ligation of gamma-glutamylcystene with glycine to form Glutathione. Amino acid sequence comparisons between the Arabidopsis and the Escherichia coli proteins suggested that a region, identified as a small flexible loop that covers the active site of the E. coli protein, might be conserved in the eukaryotic protein. Three site-directed mutations in the Arabidopsis protein were generated to test this hypothesis. Two mutations within the conserved region (Lys367/ Pro368-->Asn/Ser and Gly374-->Val) inactivated the enzyme in an in vivo assay based on cadmium resistance in S. pombe, and in an in vitro assay of the activity of the enzyme expressed in E. coli. A third mutation outside of this conserved region (Leu363-->Glu) had a smaller effect in both assays. These results are consistent with the idea that this glycine-rich loop in the Arabidopsis and E. coli proteins might serve the same function in covering the active site of the enzyme.
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Cloning of the cDNA and genomic clones for Glutathione Synthetase fromArabidopsis thaliana and complementation of agsh2 mutant in fission yeast
Plant Molecular Biology, 1996Co-Authors: Chang-lin Wang, David J OliverAbstract:Glutathione is essential for protecting plants from a range of environmental stresses, including heavy metals where it acts as a precursor for the synthesis of phytochelatins. A 1658 bp cDNA clone for Glutathione Synthetase ( gsh2 ) was isolated from Arabidopsis thaliana plants that were actively synthesizing Glutathione upon exposure to cadmium. The sequence of the clone revealed a protein with an estimated molecular mass of 53858 Da that was very similar to the protein from higher eukaryotes, was less similar to the gene from the fission yeast, Schizosaccharomyces pombe , and shared only a small region of similarity with the Escherichia coli protein. A 4.3 kb Sst I fragment containing the genomic clone for Glutathione Synthetase was also isolated and sequenced. A comparison of the cDNA and genomic sequences revealed that the gene was composed of twelve exons. When the Arabidopsis cDNA cloned in a special shuttle vector was expressed in a S. pombe mutant deficient in Glutathione Synthetase activity, the plant cDNA was able to complement the yeast mutation. Glutathione Synthetase activity was measurable in wild-type yeast cells, below detectable levels in the gsh2 ^- mutant, and restored to substantial levels by the expression of the Arabidopsis cDNA. The S. pombe mutant expressing the plant cDNA had near wild type levels of total cellular thiols,^109Cd^2+ binding activity, and cadmium resistance. Since the Arabidopsis cDNA was under control of a thiamine-repressible promoter, growth of the transformed yeast on thiamine-free medium increased expression of the cDNA resulting in increases in cadmium resistance.
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Cloning of the cDNA and genomic clones for Glutathione Synthetase from Arabidopsis thaliana and complementation of a gsh2 mutant in fission yeast.
Plant molecular biology, 1996Co-Authors: Chang-lin Wang, David J OliverAbstract:Glutathione is essential for protecting plants from a range of environmental stresses, including heavy metals where it acts as a precursor for the synthesis of phytochelatins. A 1658 bp cDNA clone for Glutathione Synthetase (gsh2) was isolated fromArabidopsis thaliana plants that were actively synthesizing Glutathione upon exposure to cadmium. The sequence of the clone revealed a protein with an estimated molecular mass of 53858 Da that was very similar to the protein from higher eukaryotes, was less similar to the gene from the fission yeast,Schizosaccharomyces pombe, and shared only a small region of similarity with theEscherichia coli protein. A 4.3 kbSstI fragment containing the genomic clone for Glutathione Synthetase was also isolated and sequenced. A comparison of the cDNA and genomic sequences revealed that the gene was composed of twelve exons.
Thomas R. Cundari - One of the best experts on this subject based on the ideXlab platform.
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The Role of Strong Electrostatic Interactions at the Dimer Interface of Human Glutathione Synthetase
The Protein Journal, 2014Co-Authors: Margarita C. Jesus, Thomas R. Cundari, Kerri D. Slavens, Khaldoon A. Barakat, Brandall L. Ingle, Bisesh Shrestha, Mary E. AndersonAbstract: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 active sites of hGS, which are 40 Å apart, display allosteric modulation by the substrate γ-glutamylcysteine (γ-GC) during the synthesis of Glutathione, a key cellular antioxidant. The two subunits interact at a relatively small dimer interface dominated by electrostatic interactions between S42, R221, and D24. Alanine scans of these sites result in enzymes with decreased activity, altered γ-GC affinity, and decreased thermal stability. Molecular dynamics simulations indicate these mutations disrupt interchain bonding and impact the tertiary structure 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.
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Valine 44 and valine 45 of human Glutathione Synthetase are key for subunit stability and negative cooperativity.
Biochemical and biophysical research communications, 2011Co-Authors: Kerri D. Slavens, Thomas R. Cundari, Teresa R. Brown, Khaldoon A. Barakat, Mary E. AndersonAbstract:It was hypothesized that residues Val44 and Val45 serve as important residues for human Glutathione Synthetase (hGS) function and stability given their location at the dimer interface of this enzyme. Computational studies suggest that mutation at Val45 has more impact on the structure and stability of hGS than does mutation at Val44. Experimentally, enzymes with mutations at the 44 and or 45 positions of hGS were prepared, purified and assayed for initial activity. Val45 position mutations (either to alanine or tryptophan) have a greater impact on enzyme activity than do mutations at Val44. Differential scanning calorimetry experiments reveal a loss of stability in all mutant enzymes, with V45 mutations being less stable than the corresponding Val44 mutations. The γ-GluABA substrate affinity remains unaltered in V44A and V45A mutant enzymes, but increases when tryptophan is introduced at either of these positions. Hill coefficients trend towards less negative cooperativity with the exception of V45W mutant hGS. These results imply that residues V44 and V45 are located along the allosteric pathway of this negatively cooperative dimeric enzyme, that their mutation impacts the allosteric pathway more than it does the active site of hGS, and that these residues (and by extension the dimer interface in which they are located) are integral to the stability of human Glutathione Synthetase.
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the role of the glycine triad in human Glutathione Synthetase
Biochemical and Biophysical Research Communications, 2010Co-Authors: Adriana Dinescu, Thomas R. Cundari, Teresa R. Brown, Sarah Barelier, Mary E. AndersonAbstract:Experimental kinetics and computational modeling of human Glutathione Synthetase (hGS) support the significant role of the G-loop glycine triad (G369, G370, G371) for activity of this ATP-grasp enzyme. Enzyme kinetic experiments indicate that G369V and G370V mutant hGS have little activity (<0.7 and 0.3%, respectively, versus wild-type hGS). However, G371V retains ∼13% of the activity of wild-type hGS. With respect to G-loop:A-loop interaction in hGS, mutations at Gly369 and Gly370 decrease ligand binding and prevent active site closure and protection. This research indicates that Gly369 and Gly370 have essential roles in hGS, while Gly371 has a lesser involvement. Implications for glycine-rich ensembles in other phosphate-binding enzymes are discussed.
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The role of the glycine triad in human Glutathione Synthetase
Biochemical and biophysical research communications, 2010Co-Authors: Adriana Dinescu, Thomas R. Cundari, Teresa R. Brown, Sarah Barelier, Mary E. AndersonAbstract:Experimental kinetics and computational modeling of human Glutathione Synthetase (hGS) support the significant role of the G-loop glycine triad (G369, G370, G371) for activity of this ATP-grasp enzyme. Enzyme kinetic experiments indicate that G369V and G370V mutant hGS have little activity (
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catalytic loop motion in human Glutathione Synthetase a molecular modeling approach
Biochemical and Biophysical Research Communications, 2007Co-Authors: Adriana Dinescu, Mary E. Anderson, Thomas R. CundariAbstract:Conformational changes of three flexible loops (G, A, and S) in human Glutathione Synthetase (hGS) arise to accommodate the substrates inside the active site. The crystal structure of hGS, a member of the ATP-grasp superfamily, has been reported only for the product-enzyme complex. To study the function of the hGS loops, molecular dynamics simulations are performed on three different conformational models: unbound enzyme, reactant-enzyme, and product-enzyme complex of hGS. The conformational changes among the three models are analyzed and the roles of the loops during the catalytic process are described. The modeled structures of hGS show that the central portions of the G- and A-loop have a double role in the reactant complex conformation: they bind the substrates and simultaneously interact with each other through an extensive network of hydrogen bonds. The present study proposes that these favorable loop-ligand and loop-loop interactions are required for opening and closing of the active site of hGS. Additionally, this research identifies important amino acid residues and explains their function within the catalytic loops of hGS.
Adriana Dinescu - One of the best experts on this subject based on the ideXlab platform.
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the role of the glycine triad in human Glutathione Synthetase
Biochemical and Biophysical Research Communications, 2010Co-Authors: Adriana Dinescu, Thomas R. Cundari, Teresa R. Brown, Sarah Barelier, Mary E. AndersonAbstract:Experimental kinetics and computational modeling of human Glutathione Synthetase (hGS) support the significant role of the G-loop glycine triad (G369, G370, G371) for activity of this ATP-grasp enzyme. Enzyme kinetic experiments indicate that G369V and G370V mutant hGS have little activity (<0.7 and 0.3%, respectively, versus wild-type hGS). However, G371V retains ∼13% of the activity of wild-type hGS. With respect to G-loop:A-loop interaction in hGS, mutations at Gly369 and Gly370 decrease ligand binding and prevent active site closure and protection. This research indicates that Gly369 and Gly370 have essential roles in hGS, while Gly371 has a lesser involvement. Implications for glycine-rich ensembles in other phosphate-binding enzymes are discussed.
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The role of the glycine triad in human Glutathione Synthetase
Biochemical and biophysical research communications, 2010Co-Authors: Adriana Dinescu, Thomas R. Cundari, Teresa R. Brown, Sarah Barelier, Mary E. AndersonAbstract:Experimental kinetics and computational modeling of human Glutathione Synthetase (hGS) support the significant role of the G-loop glycine triad (G369, G370, G371) for activity of this ATP-grasp enzyme. Enzyme kinetic experiments indicate that G369V and G370V mutant hGS have little activity (
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catalytic loop motion in human Glutathione Synthetase a molecular modeling approach
Biochemical and Biophysical Research Communications, 2007Co-Authors: Adriana Dinescu, Mary E. Anderson, Thomas R. CundariAbstract:Conformational changes of three flexible loops (G, A, and S) in human Glutathione Synthetase (hGS) arise to accommodate the substrates inside the active site. The crystal structure of hGS, a member of the ATP-grasp superfamily, has been reported only for the product-enzyme complex. To study the function of the hGS loops, molecular dynamics simulations are performed on three different conformational models: unbound enzyme, reactant-enzyme, and product-enzyme complex of hGS. The conformational changes among the three models are analyzed and the roles of the loops during the catalytic process are described. The modeled structures of hGS show that the central portions of the G- and A-loop have a double role in the reactant complex conformation: they bind the substrates and simultaneously interact with each other through an extensive network of hydrogen bonds. The present study proposes that these favorable loop-ligand and loop-loop interactions are required for opening and closing of the active site of hGS. Additionally, this research identifies important amino acid residues and explains their function within the catalytic loops of hGS.
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function of conserved residues of human Glutathione Synthetase implications for the atp grasp enzymes
Journal of Biological Chemistry, 2004Co-Authors: Adriana Dinescu, Thomas R. Cundari, Vikas S. Bhansali, Jia-li Luo, Mary E. AndersonAbstract:Glutathione Synthetase is an enzyme that belongs to the Glutathione Synthetase ATP-binding domain-like superfamily. It catalyzes the second step in the biosynthesis of Glutathione from γ-glutamylcysteine and glycine in an ATP-dependent manner. Glutathione Synthetase has been purified and sequenced from a variety of biological sources; still, its exact mechanism is not fully understood. A variety of structural alignment methods were applied and four highly conserved residues of human Glutathione Synthetase (Glu-144, Asn-146, Lys-305, and Lys-364) were identified in the binding site. The function of these was studied by experimental and computational site-directed mutagenesis. The three-dimensional coordinates for several human Glutathione Synthetase mutant enzymes were obtained using molecular mechanics and molecular dynamics simulation techniques, starting from the reported crystal structure of human Glutathione Synthetase. Consistent with circular dichroism spectroscopy, our results showed no major changes to overall enzyme structure upon residue mutation. However, semiempirical calculations revealed that ligand binding is affected by these mutations. The key interactions between conserved residues and ligands were detected and found to be essential for enzymatic activity. Particularly, the negatively charged Glu-144 residue plays a major role in catalysis.
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Function of conserved residues of human Glutathione Synthetase: implications for the ATP-grasp enzymes.
The Journal of biological chemistry, 2004Co-Authors: Adriana Dinescu, Thomas R. Cundari, Vikas S. Bhansali, Jia-li Luo, Mary E. AndersonAbstract:This article discusses human Glutathione Synthetase, an enzyme that belongs to the Glutathione Synthetase ATP-binding domain-like superfamily.