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Crystal structure of glutathione reductase Glr1 from the yeast Saccharomyces cerevisiae.

Yu J, Zhou CZ
Proteins 68 972-9 (2007)
Cited: 23 times
EuropePMC logo PMID: 17554778

Abstract

Yeast glutathione (GSH) reductase Glr1 is a dimeric flavo-oxidoreductase involved in cytoplasmic and mitochondrial redox regulatory systems. It reduces the oxidized GSH GSSG to the reduced form, GSH with NADPH as electron donor and FAD as coenzyme. Crystal structures and enzymatic mechanisms of GSH reductases from Escherichia coli and Homo sapiens have been well investigated, whereas the structural properties of yeast Glr1 remain unknown. Herein, we overexpressed Saccharomyces cerevisiae Glr1 in Pichia pastoris GS115 and determined its crystal structure at 2.40 A resolution. Although the overall structure and the active site are much conserved, obvious variety was found at the interface of Glr1 monomers when superimposed against the homolog from E. coli or human. The nonconserved C239 is exposed to the solvent and accessible to GSH or GSSG enriched in a microenvironment around the Glr1 molecules, leading to the partial and transient glutathionylation, as primarily identified from the 2Fo-Fc electron density map and further confirmed by biochemical assays. Meanwhile N278 at the vicinity of NADP-binding pocket was artificially glycosylated when heterogeneously overexpressed in P. pastoris. The highly motile oligosaccharide chain linked to N278 of the recombinant Glr1 interferes with the entry of NADPH, which results in a dramatic increase of Km for NAPDH and a significant decrease of turnover number, when compared with the native protein.

Articles - 2hqm mentioned but not cited (8)

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  2. Phosphine resistance in India is characterised by a dihydrolipoamide dehydrogenase variant that is otherwise unobserved in eukaryotes. Kaur R, Subbarayalu M, Jagadeesan R, Daglish GJ, Nayak MK, Naik HR, Ramasamy S, Subramanian C, Ebert PR, Schlipalius DI. Heredity (Edinb) 115 188-194 (2015)
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  7. The structure and activity of the glutathione reductase from Streptococcus pneumoniae. Sikanyika M, Aragão D, McDevitt CA, Maher MJ. Acta Crystallogr F Struct Biol Commun 75 54-61 (2019)
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Reviews citing this publication (4)

  1. Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Deponte M. Biochim Biophys Acta 1830 3217-3266 (2013)
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  3. The Architecture of Thiol Antioxidant Systems among Invertebrate Parasites. Guevara-Flores A, Martínez-González JJ, Rendón JL, Del Arenal IP. Molecules 22 E259 (2017)
  4. Cloneable inorganic nanoparticles. Hendricks AR, Guilliams BF, Cohen RS, Tien T, McEwen GA, Borgognoni KM, Ackerson CJ. Chem Commun (Camb) 59 8626-8643 (2023)

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  2. Characterization of a novel dithiocarbamate glutathione reductase inhibitor and its use as a tool to modulate intracellular glutathione. Seefeldt T, Zhao Y, Chen W, Raza AS, Carlson L, Herman J, Stoebner A, Hanson S, Foll R, Guan X. J Biol Chem 284 2729-2737 (2009)
  3. Expression of a glutathione reductase from Brassica rapa subsp. pekinensis enhanced cellular redox homeostasis by modulating antioxidant proteins in Escherichia coli. Kim IS, Shin SY, Kim YS, Kim HY, Yoon HS. Mol Cells 28 479-487 (2009)
  4. The glutaredoxin mono- and di-thiol mechanisms for deglutathionylation are functionally equivalent: implications for redox systems biology. Mashamaite LN, Rohwer JM, Pillay CS. Biosci Rep 35 e00173 (2015)
  5. Global Proteomic Analysis of Lysine Crotonylation in the Plant Pathogen Botrytis cinerea. Zhang N, Yang Z, Liang W, Liu M. Front Microbiol 11 564350 (2020)
  6. Metalloid Reductase of Pseudomonas moravenis Stanleyae Conveys Nanoparticle Mediated Metalloid Tolerance. Nemeth R, Neubert M, Butz ZJ, Ni TW, Ackerson CJ. ACS Omega 3 14902-14909 (2018)
  7. A functional analysis of Kluyveromyces lactis glutathione reductase. García-Leiro A, Cerdán ME, González-Siso MI. Yeast 27 431-441 (2010)
  8. Formation of two centre three electron bond by hydroxyl radical induced reaction of thiocoumarin: evidence from experimental and theoretical studies. Shinde RG, Khan AA, Barik A. Free Radic Res 53 629-640 (2019)
  9. N-biotinyl-S-(1,2-dichlorovinyl)-L-cysteine sulfoxide as a potential model for S-(1,2-dichlorovinyl)-L-cysteine sulfoxide: characterization of stability and reactivity with glutathione and kidney proteins in vitro. Irving RM, Brownfield MS, Elfarra AA. Chem Res Toxicol 24 1915-1923 (2011)
  10. The Relevance of Glutathione Reductase Inhibition by Fluoxetine to Human Health and Disease: Insights Derived from a Combined Kinetic and Docking Study. Dalmizrak O, Teralı K, Asuquo EB, Ogus IH, Ozer N. Protein J 38 515-524 (2019)
  11. Mechanistic and structural insights into the in vitro inhibitory action of hypericin on glutathione reductase purified from baker's yeast. Dalmizrak O, Teralı K, Abdullah RK, Ozer N. J Biochem Mol Toxicol 32 e22051 (2018)


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