Glutathione reductase turned into trypanothione reductase: structural analysis of an engineered change in substrate specificity.

No abstract is available for this paper.

• Publication year

  1997

• Venue

  Biochemistry

• Publication date

  1997-05-27

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1021/BI963074PPMID 9174360
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Charge is the major discriminating factor for glutathione reductase versus trypanothione reductase inhibitors.

  1996cited by this paper
• Crystal structure of the Trypanosoma cruzi trypanothione reductase·mepacrine complex

  1996cited by this paper
• The Structure of Trypanosoma cruzitrypanothione Reductase in the Oxidized and NADPH Reduced State

  1994cited by this paper
• Substrate binding and catalysis by glutathione reductase as derived from refined enzyme: substrate crystal structures at 2 A resolution.

  1994cited by this paper
• Structure of glutathione reductase from escherichia coli at 1.86 Å resolution: Comparison with the enzyme from human erythrocytes

  1994cited by this paper
• Substrate interactions between trypanothione reductase and N1-glutathionylspermidine disulphide at 0.28-nm resolution.

  1993cited by this paper
• SETOR: hardware-lighted three-dimensional solid model representations of macromolecules.

  1993cited by this paper
• Metabolism and functions of trypanothione in the Kinetoplastida.

  1992cited by this paper
• Active site of trypanothione reductase. A target for rational drug design.

  1992cited by this paper
• Mutational analysis of parasite trypanothione reductase: acquisition of glutathione reductase activity in a triple mutant.

  1991cited by this paper
• Improved methods for building protein models in electron density maps and the location of errors in these models.

  1991cited by this paper
• Engineering the substrate specificity of glutathione reductase toward that of trypanothione reduction.

  1991cited by this paper
• Redox enzyme engineering: conversion of human glutathione reductase into a trypanothione reductase.

  1991cited by this paper
• X-ray structure of trypanothione reductase from Crithidia fasciculata at 2.4-A resolution.

  1991cited by this paper
• Enzyme evolution. Déjà vu all over again.

  1991cited by this paper
• Molecular studies on trypanothione reductase, a target for antiparasitic drugs.

  1991cited by this paper
• The binding of the retro-analogue of glutathione disulfide to glutathione reductase.

  1991cited by this paper
• Cloning, sequencing, overproduction and purification of trypanothione reductase from Trypanosoma cruzi.

  1991cited by this paper
• Random silent mutagenesis in the initial triplets of the coding region: a technique for adapting human glutathione reductase-encoding cDNA to expression in Escherichia coli.

  1990cited by this paper
• Inactivation-reactivation of two-electron reduced Escherichia coli glutathione reductase involving a dimer-monomer equilibrium.

  1989cited by this paper
• Trypanothione reductase from Trypanosoma cruzi. Catalytic properties of the enzyme and inhibition studies with trypanocidal compounds.

  1989cited by this paper
• A crystallographic study of the glutathione binding site of glutathione reductase at 0.3-nm resolution.

  1989cited by this paper
• Trypanothione reductase of Trypanosoma congolense: gene isolation, primary sequence determination, and comparison to glutathione reductase.

  1988cited by this paper
• Crystallographic R Factor Refinement by Molecular Dynamics

  1987cited by this paper
• Trypanothione reductase from Trypanosoma cruzi. Purification and characterization of the crystalline enzyme.

  1987cited by this paper
• Refined structure of glutathione reductase at 1.54 A resolution.

  1987cited by this paper
• Purification and characterization of trypanothione reductase from Crithidia fasciculata, a newly discovered member of the family of disulfide-containing flavoprotein reductases.

  1986cited by this paper
• Glutathione reductase from Escherichia coli: cloning and sequence analysis of the gene and relationship to other flavoprotein disulfide oxidoreductases.

  1986cited by this paper
• Identification of a novel, thiol-containing co-factor essential for glutathione reductase enzyme activity in trypanosomatids.

  1985cited by this paper
• Crystallization of macromolecules: general principles.

  1985cited by this paper
• Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids.

  1985cited by this paper
• Glutathione.

  1983cited by this paper
• The catalytic mechanism of glutathione reductase as derived from x-ray diffraction analyses of reaction intermediates.

  1983cited by this paper
• The structure of the flavoenzyme glutathione reductase

  1978cited by this paper
• Glutathione reductase from human erythrocytes. Catalytic properties and aggregation.

  1976cited by this paper
• Crystals of human erythrocyte glutathione reductase

  1975cited by this paper
• Isolation, characterization, and turnover of glutathionylspermidine from Escherichia coli.

  1975cited by this paper

• Photoactivity of Pluronic® F-127 nanoencapsulated hypericin against Leishmania: A promising approach for cutaneous leishmaniasis.

  2025cites this paper
• Building on a theme: The redox hierarchy of pyridine nucleotide-disulfide oxidoreductases.

  2024cites this paper
• State-of-the-art Review on the Antiparasitic Activity of Benzimidazole-based Derivatives: Facing Malaria, Leishmaniasis, and Trypanosomiasis

  2023cites this paper
• Experimental structure based drug design (SBDD) applications for anti‐leishmanial drugs: A paradigm shift?

  2023cites this paper
• Tackling Sleeping Sickness: Current and Promising Therapeutics and Treatment Strategies

  2023cites this paper
• In Vitro and In Vivo Trypanocidal Efficacy of Nitrofuryl- and Nitrothienylazines

  2023cites this paper
• Participation of Oxidative Stress in the Activity of Compounds Isolated from Eleutherine plicata Herb

  2023cites this paper
• Systems pharmacology aiding benzimidazole scaffold as potential lead compounds against leishmaniasis for functional therapeutics.

  2022cites this paper
• Cadmium binding to antioxidant enzymes: in silico study

  2021cites this paper
• A “Golden Age” for the discovery of new antileishmanial agents: Current status of leishmanicidal gold complexes and prospective targets beyond the trypanothione system

  2021cites this paper
• Anti-human lung cancer activities and survey of gluthation reductase and gluthation S transferase inhibition properties with molecular modeling studies of 2′-Hydroxy-5′-methyl-3′-nitroacetophenone: A pre-clinical trial study

  2021cites this paper
• Thiohydantoins as anti-leishmanial agents: n vitro biological evaluation and multi-target investigation by molecular docking studies

  2020cites this paper
• Targeting Trypanothione Reductase, a Key Enzyme in the Redox Trypanosomatid Metabolism, to Develop New Drugs against Leishmaniasis and Trypanosomiases

  2020cites this paper
• The Biological Impact of Oxidative Metabolism in Trypanosomatid Parasites: What Is the Perfect Balance Between Reactive Species Production and Antioxidant Defenses?

  2019cites this paper
• The role of thiols in antioxidant systems.

  2019cites this paper
• Understanding the Cross-Talk of Redox Metabolism and Fe-S Cluster Biogenesis in Leishmania Through Systems Biology Approach

  2019cites this paper
• Oxidative Stress in Microbial Diseases

  2019cites this paper
• Molecular insights into trypanothione reductase‐inhibitor interaction: A structure‐based review

  2018cites this paper
• The Architecture of Thiol Antioxidant Systems among Invertebrate Parasites

  2017cites this paper
• Polyamine-Based Thiols in Trypanosomatids: Evolution, Protein Structural Adaptations, and Biological Functions

  2017cites this paper
• Synthesis and in vitro antikinetoplastid activity of polyamine-hydroxybenzotriazole conjugates.

  2017cites this paper
• Molecular docking to explore the possible binding mode of potential inhibitors of thioredoxin glutathione reductase

  2015cites this paper
• Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease.

  2015cites this paper
• Key proteins in the polyamine-trypanothione pathway as drug targets against Trypanosoma cruzi.

  2014cites this paper
• Thioredoxin Reductase and its Inhibitors

  2014cites this paper
• Screening approaches towards trypanothione reductase.

  2013cites this paper
• Inhibition of Leishmania infantum Trypanothione Reductase by Azole‐Based Compounds: a Comparative Analysis with Its Physiological Substrate by X‐ray Crystallography

  2013cites this paper
• Improved Inhibitors of Trypanothione Reductase by Combination of Motifs: Synthesis, Inhibitory Potency, Binding Mode, and Antiprotozoal Activities

  2011cites this paper
• New World trypanosomiasis.

  2010cites this paper
• Targeting trypanothione metabolism in trypanosomatid human parasites.

  2010cites this paper
• Insights into the redox biology of Trypanosoma cruzi: Trypanothione metabolism and oxidant detoxification.

  2008cites this paper
• Comprehensive structural classification of ligand-binding motifs in proteins.

  2008cites this paper
• RNA interference: a pathway to drug target identification and validation in trypanosome

  2008cites this paper
• A fluoro analogue of the menadione derivative 6-[2'-(3'-methyl)-1',4'-naphthoquinolyl]hexanoic acid is a suicide substrate of glutathione reductase. Crystal structure of the alkylated human enzyme.

  2006cites this paper
• Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new drug targets in trypanosomes and malaria-causing plasmodia.

  2005cites this paper
• Irreversible inactivation of trypanothione reductase by unsaturated Mannich bases: a divinyl ketone as key intermediate.

  2005cites this paper
• Inhibitors of Trypanosoma cruzi trypanothione reductase revealed by virtual screening and parallel synthesis.

  2005cites this paper
• Dithiolproteine als Hüter des intrazellulären Redoxmilieus bei Parasiten: alte und neue Wirkstoff‐Targets bei Trypanosomiasis und Malaria

  2005cites this paper
• Flavoprotein disulfide reductases: advances in chemistry and function.

  2004cites this paper
• Identification and Purity Control of Thioacridine Derivatives by Gas and Capillary Liquid Chromatography with Mass Spectrometric Detection

  2004cites this paper
• Capillary zone electrophoretic assay of biologically active thioacridine derivatives

  2003cites this paper
• The Role of Glutathione Peroxidases in Trypanosomatids

  2003cites this paper
• The diversity and evolution of thioredoxin reductase: new perspectives.

  2002cites this paper
• Trypanosomal Antioxidants and Emerging Aspects of Redox Regulation in the Trypanosomatids

  2002cites this paper
• Use of Indirect Site-directed Mutagenesis to Alter the Substrate Specificity of Methylamine Dehydrogenase*

  2002cites this paper
• Trypanothione as a target in the design of antitrypanosomal and antileishmanial agents.

  2001cites this paper
• Enzyme redesign.

  2001cites this paper
• Probing molecular function of trypanosomal sialidases: single point mutations can change substrate specificity and increase hydrolytic activity.

  2001cites this paper
• Energetic consequences of accommodating a bulkier ligand at the active site of medium chain acyl-CoA dehydrogenase by creating a complementary enzyme site cavity.

  2000cites this paper
• Glutathione and trypanothione in parasitic hydroperoxide metabolism.

  1999cites this paper
• Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors.

  1999cites this paper
• Glutathione and its role in cellular functions.

  1999cites this paper
• Inhibition of Trypanosoma cruzi trypanothione reductase by acridines: kinetic studies and structure-activity relationships.

  1999cites this paper
• Design, synthesis, and biochemical evaluation of phosphonate and phosphonamidate analogs of glutathionylspermidine as inhibitors of glutathionylspermidine synthetase/amidase from Escherichia coli.

  1997cites this paper