The Role of S-Glutathionylation in Health and Disease: A Bird's Eye View.

Protein glutathionylation is a reversible post-translational modification that involves the attachment of glutathione to cysteine residues. It plays a role in the regulation of several cellular processes and protection against oxidative damage. Glutathionylation (GS-ylation) modulates protein function, inhibits or enhances enzymatic activity, maintains redox homeostasis, and shields several proteins from irreversible oxidative stress.

An overview of bats microbiota and its implication in transmissible diseases.

Recent pandemic events have raised the attention of the public on the interactions between human and environment, with particular regard to the more and more feasible transmission to humans of micro-organisms hosted by wild-type species, due to the increasing interspecies contacts originating from human's activities. Bats, due to their being flying mammals and their increasing promiscuity with humans, have been recognized as hosts frequently capable of transmitting disease-causing microorganisms. Therefore, it is of considerable interest and importance to have a picture as clear as possible of the microorganisms that are hosted by bats.

Structural Characterization of the Xi Class Glutathione Transferase From the Haloalkaliphilic Archaeon .

Xi class glutathione transferases (GSTs) are a recently identified group, within this large superfamily of enzymes, specifically endowed with glutathione-dependent reductase activity on glutathionyl-hydroquinone. Enzymes belonging to this group are widely distributed in bacteria, fungi, and plants but not in higher eukaryotes. Xi class GSTs are also frequently found in archaea and here we focus on the enzyme produced by the extreme haloalkaliphilic archaeon (NmGHR).

Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases.

Glutathione transferase classical GSH conjugation activity plays a critical role in cellular detoxification against xenobiotics and noxious compounds as well as against oxidative stress. However, this feature is also exploited by cancer cells to acquire drug resistance and improve their survival. As a result, various members of the family were found overexpressed in a number of different cancers.

Escherichia coli in Europe: an overview.

Escherichia coli remains one of the most frequent causes of several common bacterial infections in humans and animals. E. coli is the prominent cause of enteritis, urinary tract infection, septicaemia and other clinical infections, such as neonatal meningitis.

Identification of an elongation factor 1Bγ protein with glutathione transferase activity in both yeast and mycelial morphologies from human pathogenic Blastoschizomyces capitatus.

Blastoschizomyces capitatus is an uncommon, opportunistic pathogenic fungus, which causes invasive and disseminated infections. This microorganism is normally present in both environmental and normal human flora. Within a host, B.

Distribution of glutathione transferases in Gram-positive bacteria and Archaea.

Glutathione transferases (GSTs) have been widely studied in Gram-negative bacteria and the structure and function of several representatives have been elucidated. Conversely, limited information is available about the occurrence, classification and functional features of GSTs both in Gram-positive bacteria and in Archaea. An analysis of 305 fully-sequenced Gram-positive genomes highlights the presence of 49 putative GST genes in the genera of both Firmicutes and Actinobacteria phyla.

Characterization of the hydrophobic substrate-binding site of the bacterial beta class glutathione transferase from Proteus mirabilis.

Since their discovery, bacterial glutathione (GSH)transferases have been characterized in terms of their ability to catalyse a variety of different reactions on a large set of toxic molecules of xenobiotic or endobiotic origin. Furthermore the contribution of different residues in the GSH-binding site to GSH activation has been extensively investigated. Little is known, however, about the contribution to catalysis and overall stability of single residues shaping the hydrophobic co-substrate binding site (H-site).

A conserved hydrogen-bond network stabilizes the structure of Beta class glutathione S-transferases.

We identified a network of hydrogen bonds that is conserved in the structures of bacterial Beta class glutathione S-transferases (GSTs). It is formed by three residues: a serine, a histidine and a glutamate, together with a water molecule that links the serine with the histidine. This network connects the first helix of the N-terminal glutaredoxin-like domain with the last helix of the C-terminal GST-specific all helical domain.

Glutathione transferases in bacteria.

Bacterial glutathione transferases (GSTs) are part of a superfamily of enzymes that play a key role in cellular detoxification. GSTs are widely distributed in prokaryotes and are grouped into several classes. Bacterial GSTs are implicated in a variety of distinct processes such as the biodegradation of xenobiotics, protection against chemical and oxidative stresses and antimicrobial drug resistance.

Cysteine 10 is critical for the activity of Ochrobactrum anthropi glutathione transferase and its mutation to alanine causes the preferential binding of glutathione to the H-site.

The role of the evolutionarily conserved residue Cys10 in Ochrobactrum anthropi glutathione transferase (OaGST) has been examined by replacing it with an alanine. A double mutant C10A/S11A was also prepared. The effect of the replacements on the coniugating and thiotransferase activities, and on the thermal and chemical stability of the enzyme was analyzed.

Role of Ser11 in the stabilization of the structure of Ochrobactrum anthropi glutathione transferase.

GSTs (glutathione transferases) are a multifunctional group of enzymes, widely distributed and involved in cellular detoxification processes. In the xenobiotic-degrading bacterium Ochrobactrum anthropi, GST is overexpressed in the presence of toxic concentrations of aromatic compounds such as 4-chlorophenol and atrazine. We have determined the crystal structure of the GST from O.

Evolutionarily conserved structural motifs in bacterial GST (glutathione S-transferase) are involved in protein folding and stability.

The bacterium Proteus mirabilis expresses a cytosolic class beta glutathione S-transferase (PmGST B1-1) that is part of a family of multifunctional detoxication enzymes. Like other cytosolic GSTs, PmGST B1-1 possesses two local structural motifs, an N-capping box and a hydrophobic staple motif, both of which are located between amino acids 151 and 156. The N-capping box consists of a reciprocal hydrogen bonding interaction of Thr152 with Asp155, whereas the hydrophobic staple motif consists of a hydrophobic interaction between Phe151 and Ala156.

Contribution of the two conserved tryptophan residues to the catalytic and structural properties of Proteus mirabilis glutathione S-transferase B1-1.

PmGSTB1-1 (Proteus mirabilis glutathione S-transferase B1-1) has two tryptophan residues at positions 97 and 164 in each monomer. Structural data for this bacterial enzyme indicated that Trp97 is positioned in the helix a4, whereas Trp164 is located at the bottom of the helix a6 in the xenobiotic-binding site. To elucidate the role of the two tryptophan residues they were replaced by site-directed mutagenesis.

Proteus mirabilis glutathione S-transferase B1-1 is involved in protective mechanisms against oxidative and chemical stresses.

We investigated the effects of several xenobiotics, including antimicrobial agents and general stress factors such as starvation, heat and osmotic shock, on the modulation of expression of Proteus mirabilis glutathione S-transferase B1-1 (PmGST B1-1). The level of expression of PmGST B1-1 was established by both Western- and Northern-blot experiments. Our results show that several compounds can modulate expression of PmGST B1-1.

Properties and utility of the peculiar mixed disulfide in the bacterial glutathione transferase B1-1.

Bacterial glutathione transferases appear to represent an evolutionary link between the thiol:disulfide oxidoreductase and glutathione transferase superfamilies. In particular, the observation of a mixed disulfide in the active site of Proteus mirabilis glutathione transferase B1-1 is a feature that links the two families. This peculiar mixed disulfide between Cys10 and one GSH molecule has been studied by means of ESR spectroscopy, stopped-flow kinetic analysis, radiochemistry, and site-directed mutagenesis.

Glutamic acid-65 is an essential residue for catalysis in Proteus mirabilis glutathione S-transferase B1-1.

The functional role of three conserved amino acid residues in Proteus mirabilis glutathione S-transferase B1-1 (PmGST B1-1) has been investigated by site-directed mutagenesis. Crystallographic analyses indicated that Glu(65), Ser(103) and Glu(104) are in hydrogen-bonding distance of the N-terminal amino group of the gamma-glutamyl moiety of the co-substrate, GSH. Glu(65) was mutated to either aspartic acid or leucine, and Ser(103) and Glu(104) were both mutated to alanine.

GSTB1-1 from Proteus mirabilis: a snapshot of an enzyme in the evolutionary pathway from a redox enzyme to a conjugating enzyme.

The native form of the bacterial glutathione transferase B1-1 (EC ) is characterized by one glutathione (GSH) molecule covalently linked to Cys-10. This peculiar disulfide, only found in the Beta and Omega class glutathione S-transferases (GSTs) but absent in all other GSTs, prompts questions about its role and how GSH can be activated and utilized in the reaction normally performed by GSTs. Stopped-flow and spectroscopic experiments suggest that, in the native enzyme (GSTB1-1ox), a second GSH molecule is present, albeit transiently, in the active site.