Chemical modification at subunit 1 of rat kidney Alpha class glutathione transferase with 2,3,5,6-tetrachloro-1,4-benzoquinone: Close structural connectivity between glutathione conjugation activity and non-substrate ligand binding

2006 ◽  
Vol 71 (11) ◽  
pp. 1629-1636 ◽  
Author(s):  
Siobhan M. O'Sullivan ◽  
Ronan M. McCarthy ◽  
Melissa A. Vargo ◽  
Roberta F. Colman ◽  
David Sheehan
Keyword(s):  
Ligand Binding ◽  
Chemical Modification ◽  
Glutathione Transferase ◽  
Rat Kidney ◽  
Structural Connectivity ◽  
Glutathione Conjugation

Glutathione conjugation of the fluorophotometric epoxide substrate, 7- glycidoxycoumarin (GOC), by rat liver glutathione transferase isoenzymes

1989 ◽  
Vol 38 (16) ◽  
pp. 2609-2613 ◽  
Author(s):  
Akira Hiratsuka ◽  
Akihiro Yokoi ◽  
Noriyuki Sebata ◽  
Tadashi Watabe ◽  
kimihiko Satoh ◽  
...  
Keyword(s):  
Rat Liver ◽  
Glutathione Transferase ◽  
Liver Glutathione ◽  
Glutathione Conjugation

scholarly journals Influence of the H-site residue 108 on human glutathione transferase P1-1 ligand binding: Structure-thermodynamic relationships and thermal stability

2009 ◽  
Vol 18 (12) ◽  
pp. 2454-2470 ◽  
Author(s):  
Indalecio Quesada-Soriano ◽  
Lorien J. Parker ◽  
Alessandra Primavera ◽  
Juan M. Casas-Solvas ◽  
Antonio Vargas-Berenguel ◽  
...  
Keyword(s):  
Thermal Stability ◽  
Ligand Binding ◽  
Glutathione Transferase ◽  
Thermodynamic Relationships ◽  
Binding Structure

Involvement of Different Human Glutathione Transferase Isoforms in the Glutathione Conjugation of Reactive Metabolites of Troglitazone

2011 ◽  
Vol 39 (12) ◽  
pp. 2290-2297 ◽  
Author(s):  
Ran Okada ◽  
Kazuya Maeda ◽  
Takahito Nishiyama ◽  
Shinsuke Aoyama ◽  
Zenzaburo Tozuka ◽  
...  
Keyword(s):  
Glutathione Transferase ◽  
Reactive Metabolites ◽  
Glutathione Conjugation

scholarly journals Chemical modification of rat liver microsomal glutathione transferase defines residues of importance for catalytic function

1990 ◽  
Vol 272 (2) ◽  
pp. 479-484 ◽  
Author(s):  
C Andersson ◽  
R Morgenstern
Keyword(s):  
Chemical Modification ◽  
Rat Liver ◽  
Active Site ◽  
Glutathione Transferase ◽  
Amino Acid Residues ◽  
Active Site Residues ◽  
Histidine Residues ◽  
Catalytic Function ◽  
Low Efficiency ◽  
Microsomal Glutathione

Amino acid residues that are essential for the activity of rat liver microsomal glutathione transferase have been identified using chemical modification with various group-selective reagents. The enzyme reconstituted into phosphatidylcholine liposomes does not require stabilization with glutathione for activity (in contrast with the purified enzyme in detergent) and can thus be used for modification of active-site residues. Protection by the product analogue and inhibitor S-hexylglutathione was used as a criterion for specificity. It was shown that the histidine-selective reagent diethylpyrocarbonate inactivated the enzyme and that S-hexylglutathione partially protected against this inactivation. All three histidine residues in microsomal glutathione transferase could be modified, albeit at different rates. Inactivation of 90% of enzyme activity was achieved within the time period required for modification of the most reactive histidine, indicating the functional importance of this residue in catalysis. The arginine-selective reagents phenylglyoxal and 2,3-butanedione inhibited the enzyme, but the latter with very low efficiency; therefore no definitive assignment of arginine as essential for the activity of microsomal glutathione transferase can be made. The amino-group-selective reagents 2,4,6-trinitrobenzenesulphonate and pyridoxal 5′-phosphate inactivated the enzyme. Thus histidine residues and amino groups are suggested to be present in the active site of the microsomal glutathione transferase.

scholarly journals A rush to explore protein–ligand electrostatic interaction energy with Charger

2021 ◽  
Vol 77 (10) ◽  
pp. 1292-1304 ◽  
Author(s):  
Vedran Vuković ◽  
Theo Leduc ◽  
Zoe Jelić-Matošević ◽  
Claude Didierjean ◽  
Frédérique Favier ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Interaction Energy ◽  
Electrostatic Interaction ◽  
Glutathione Transferase ◽  
Multipole Moment ◽  
Point Of View ◽  
Electrostatic Energy ◽  
Electron Densities ◽  
Acta Cryst ◽  
Ligand Interaction

The mutual penetration of electron densities between two interacting molecules complicates the computation of an accurate electrostatic interaction energy based on a pseudo-atom representation of electron densities. The numerical exact potential and multipole moment (nEP/MM) method is time-consuming since it performs a 3D integration to obtain the electrostatic energy at short interaction distances. Nguyen et al. [(2018), Acta Cryst. A74, 524–536] recently reported a fully analytical computation of the electrostatic interaction energy (aEP/MM). This method performs much faster than nEP/MM (up to two orders of magnitude) and remains highly accurate. A new program library, Charger, contains an implementation of the aEP/MM method. Charger has been incorporated into the MoProViewer software. Benchmark tests on a series of small molecules containing only C, H, N and O atoms show the efficiency of Charger in terms of execution time and accuracy. Charger is also powerful in a study of electrostatic symbiosis between a protein and a ligand. It determines reliable protein–ligand interaction energies even when both contain S atoms. It easily estimates the individual contribution of every residue to the total protein–ligand electrostatic binding energy. Glutathione transferase (GST) in complex with a benzophenone ligand was studied due to the availability of both structural and thermodynamic data. The resulting analysis highlights not only the residues that stabilize the ligand but also those that hinder ligand binding from an electrostatic point of view. This offers new perspectives in the search for mutations to improve the interaction between the two partners. A proposed mutation would improve ligand binding to GST by removing an electrostatic obstacle, rather than by the traditional increase in the number of favourable contacts.

Enzymatic Detoxification using Lipophilic Hollow-Fiber Membranes: IV. Glutathione Conjugation Reactions

1989 ◽  
Vol 12 (2) ◽  
pp. 121-128 ◽  
Author(s):  
D. Tsikas ◽  
G. Brunner
Keyword(s):  
Hollow Fiber ◽  
Glutathione Transferase ◽  
Hollow Fiber Membrane ◽  
Styrene Oxide ◽  
Acid Methyl Ester ◽  
Covalent Immobilization ◽  
Transferase Activity ◽  
Enzyme Preparations ◽  
Glutathione Conjugation ◽  
Epoxystearic Acid

A hollow-fiber technique was used in the enzymatic glutathione conjugation of lipophilic toxins. Native enzyme was circulated on the external side of a lipophilic hollow-fiber membrane while the toxin-containing media (blood, plasma or aqueous solution) were circulated inside the fiber. Glutathione conjugation reactions were catalyzed by rat liver cytosol, with a specific glutathione transferase activity of 40 nmol/min/mg protein (acceptor: 1,2-epoxy-3-(p-nitrophenoxy)propane). Clearance rates of 1,2-epoxy-3-(p-nitrophenoxy)propane, phenylglycidether, styrene oxide, cis-9, 10-epoxystearic acid, cis-9, 10-epoxystearic acid methyl ester, 5a, 6a-cholesterol oxide, 16-, 17a-pregnenolone oxide, and p-nitrobenzylchloride were 10.44, 13.37, 32.25, 7.60, 7.31, 3.92, 4.20 and 29.24 nmol/mg protein/h/cm2 hollow-fiber surface respectively. This technique makes possible glutathione conjugation reactions with crude enzyme preparations over long periods without loss of activity from covalent immobilization and without loss of cofactor from (auto)oxidation. The lipophilic membrane ensures the absence of hemolysis, immunological hazards and hormone loss, while elimination of the toxin is not impaired.

Chemical modification of human placental glutathione transferase by pyridoxal 5′-phosphate

1992 ◽  
Vol 1121 (1-2) ◽  
pp. 167-172 ◽  
Author(s):  
Mario Lo Bello ◽  
Raffaele Petruzzelli ◽  
Lucia Reale ◽  
Giorgio Ricci ◽  
Donatella Barra ◽  
...  
Keyword(s):  
Chemical Modification ◽  
Glutathione Transferase
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