Trimeric microsomal glutathione transferase 2 displays one third of the sites reactivity

Ahmad, Shabbir; Thulasingam, Madhuranayaki; Palombo, Isolde; Daley, Daniel O.; Johnson, Kenneth A.; Morgenstern, Ralf; Haeggström, Jesper Z.; Rinaldo-Matthis, Agnes

doi:10.1016/j.bbapap.2015.06.003

Cited by 19 publications

(17 citation statements)

References 20 publications

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“…Both catalyse the conjugation of GSH to leukotriene A4. Whereas LTC4S shows an all sites reactivity 32 , MGST2 shows a 1/3 sites reactivity 33 akin to MGST1. The loop between TM1 and TM2 forms a lid over the active site in LTC4S and would have to fold away to allow for an extended conformation of GSH.…”

Section: Discussionmentioning

confidence: 99%

“…It was observed that the most well studied membrane bound GST, microsomal glutathione transferase 1 (MGST1, EC number: 2.5.1.18) shared similarities with leukotriene C4 synthase (LTC4S, EC number: 4.4.1.20), catalyzing the conjugation reaction between leukotriene (LT) A4 and GSH. Recently, characterization of MGST2 has revealed similarities also to this enzyme regarding substrate specificity and third-of-the-sites-reaction mechanism 8 , 9 . It is now well established that MGST1, MGST2 and LTC4S belong to the membrane associated proteins in eicosanoid and glutathione metabolism (MAPEG) superfamily 7 .…”

Section: Introductionmentioning

confidence: 99%

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Dead-end complex, lipid interactions and catalytic mechanism of microsomal glutathione transferase 1, an electron crystallography and mutagenesis investigation

Kuang

Purhonen

Ålander

et al. 2017

Sci Rep

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Microsomal glutathione transferase 1 (MGST1) is a detoxification enzyme belonging to the Membrane Associated Proteins in Eicosanoid and Glutathione Metabolism (MAPEG) superfamily. Here we have used electron crystallography of two-dimensional crystals in order to determine an atomic model of rat MGST1 in a lipid environment. The model comprises 123 of the 155 amino acid residues, two structured phospholipid molecules, two aliphatic chains and one glutathione (GSH) molecule. The functional unit is a homotrimer centered on the crystallographic three-fold axes of the unit cell. The GSH substrate binds in an extended conformation at the interface between two subunits of the trimer supported by new in vitro mutagenesis data. Mutation of Arginine 130 to alanine resulted in complete loss of activity consistent with a role for Arginine 130 in stabilizing the strongly nucleophilic GSH thiolate required for catalysis. Based on the new model and an electron diffraction data set from crystals soaked with trinitrobenzene, that forms a dead-end Meisenheimer complex with GSH, a difference map was calculated. The map reveals side chain movements opening a cavity that defines the second substrate site.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dead-end complex, lipid interactions and catalytic mechanism of microsomal glutathione transferase 1, an electron crystallography and mutagenesis investigation

Kuang

Purhonen

Ålander

et al. 2017

Sci Rep

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“…The remaining proteins-encoding mRNAs have not been characterized functionally, five were up-regulated: Fam229b had the largest fold change with training; RGD1566265 is located on the X chromosome; Mgst2 catalyzes production of the C4 leukotriene (Ahmad et al 2015); Magee2 and Dcbld1 may both be predicted to have roles in new neuronal connections, but definitive studies are not available. The down-regulated protein Gng12, the G protein gamma subunit12, is associated with filamentous actin and observed in both glia and postsynaptic neuronal compartments.…”

Section: Discussionmentioning

confidence: 99%

Learning-induced mRNA alterations in olfactory bulb mitral cells in neonatal rats

et al. 2020

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In the olfactory bulb, a cAMP/PKA/CREB-dependent form of learning occurs in the first week of life that provides a unique mammalian model for defining the epigenetic role of this evolutionarily ancient plasticity cascade. Odor preference learning in the week-old rat pup is rapidly induced by a 10-min pairing of odor and stroking. Memory is demonstrable at 24 h, but not 48 h, posttraining. Using this paradigm, pups that showed peppermint preference 30 min posttraining were sacrificed 20 min later for laser microdissection of odor-encoding mitral cells. Controls were given odor only. Microarray analysis revealed that 13 nonprotein-coding mRNAs linked to mRNA translation and splicing and 11 protein-coding mRNAs linked to transcription differed with odor preference training. MicroRNA23b, a translation inhibitor of multiple plasticity-related mRNAs, was down-regulated. Protein-coding transcription was up-regulated for Sec23b, Clic2, Rpp14, Dcbld1, Magee2, Mstn, Fam229b, RGD1566265, and Mgst2. Gng12 and Srcg1 mRNAs were down-regulated. Increases in Sec23b, Clic2, and Dcbld1 proteins were confirmed in mitral cells in situ at the same time point following training. The protein-coding changes are consistent with extracellular matrix remodeling and ryanodine receptor involvement in odor preference learning. A role for CREB and AP1 as triggers of memory-related mRNA regulation is supported. The small number of gene changes identified in the mitral cell input/output link for 24 h memory will facilitate investigation of the nature, and reversibility, of changes supporting temporally restricted long-term memory.

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“…Q8PG02) is considered to be one of the essential Xac genes required for plant-pathogen interactions. Xac3819 encodes a polypeptide of 207 aminoacid residues representing an uncharacterized and unclassified glutathione transferase (XacGST), historically also called glutathione S-transferase (EC 2.5.1.18; Ahmad et al, 2015). The Xac genome contains 11 uncharacterized and unclassified GST genes (Xac0894, Xac1007, Xac1299, Xac1461, Xac1474, Xac2230, Xac2394, Xac2460, Xac3819, Xac4047 and Xac4352;da Silva et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Structural and biochemical characterization of a glutathione transferase from the citrus canker pathogenXanthomonas

Hilario

Keyser

Фан

2020

Acta Cryst Sect D Struct Biol

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The genus Xanthomonas comprises several cosmopolitan plant-pathogenic bacteria that affect more than 400 plant species, most of which are of economic interest. Citrus canker is a bacterial disease that affects citrus species, reducing fruit yield and quality, and is caused by the bacterium Xanthomonas citri subsp. citri (Xac). The Xac3819 gene, which has previously been reported to be important for citrus canker infection, encodes an uncharacterized glutathione S-transferase (GST) of 207 amino-acid residues in length (XacGST). Bacterial GSTs are implicated in a variety of metabolic processes such as protection against chemical and oxidative stresses. XacGST shares high sequence identity (45%) with the GstB dehalogenase from Escherichia coli O6:H1 strain CFT073 (EcGstB). Here, XacGST is reported to be able to conjugate glutathione (GSH) with bromoacetate with a K m of 6.67 ± 0.77 mM, a k cat of 42.69 ± 0.32 s−1 and a k cat/K m of 6.40 ± 0.72 mM −1 s−1 under a saturated GSH concentration (3.6 mM). These values are comparable to those previously reported for EcGstB. In addition, crystal structures of XacGST were determined in the apo form (PDB entry 6nxv) and in a GSH-bound complex (PDB entry 6nv6). XacGST has a canonical GST-like fold with a conserved serine residue (Ser12) at the GSH-binding site near the N-terminus, indicating XacGST to be a serine-type GST that probably belongs to the theta-class GSTs. GSH binding stabilizes a loop of about 20 residues containing a helix that is disordered in the apo XacGST structure.

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Trimeric microsomal glutathione transferase 2 displays one third of the sites reactivity

Cited by 19 publications

References 20 publications

Dead-end complex, lipid interactions and catalytic mechanism of microsomal glutathione transferase 1, an electron crystallography and mutagenesis investigation

Dead-end complex, lipid interactions and catalytic mechanism of microsomal glutathione transferase 1, an electron crystallography and mutagenesis investigation

Learning-induced mRNA alterations in olfactory bulb mitral cells in neonatal rats

Structural and biochemical characterization of a glutathione transferase from the citrus canker pathogenXanthomonas

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