1,721,101 research outputs found
Glutathione transferases in bacteria.
No full textBacterial 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. In addition to their role in detoxification, bacterial GSTs are also involved in a variety of distinct metabolic processes such as the biotransformation of dichloromethane, the degradation of lignin and atrazine, and the reductive dechlorination of pentachlorophenol. This review article summarizes the current status of knowledge regarding the functional and structural properties of bacterial GSTs
Vitamin A, beta carotene, licopene and vitamin E levels in human preovulatory follicular fluid
No full textInteraction of bacterial glutathione transferase with hemin.
No full textGlutathione transferases (GSTs, EC 2.5.1.18) are pivotal enzymes for detoxification processes in eukaryotes and prokaryotes (1, 2). GSTs catalyse glutathione conjugation to a broad spectrum of compounds. In addition, functions not related to detoxification have been discovered for GSTs including steroid biosynthesis, signal transduction and intracellular transport (1).
Hemin has been shown to be hazardous to the cell membrane because it inserts into the lipid bilayer and binds to membrane proteins. These interactions may cause membrane changes, which may lead to cellular lysis.
The ability of several eukaryotic GSTs from pluricellular and unicellular organisms to interact with hemin has been widely investigated (3, 4), and this compound was shown to bind the enzyme with high affinity (3, 4).
To verify if this interaction is a prerogative of eukaryotic GSTs or it has a general significance, we studied the binding of hemin to Proteus mirabilis GST (PmGST), a representative bacterial GST belonging to the Beta class. The interaction was studied by means of inhibition assays and fluorescence spectroscopy. Results obtained indicate that PmGST binds hemin efficiently, with a considerable quenching of the intrinsic fluorescence of PmGST. Furthermore, hemin was found to be a strong inhibitor of GST conjugation activity
Glutatione transferasi nel micete opportunista Blastoschizomyces capitatus.
No full textBlastoschizomyces capitatus è un patogeno fungino emergente responsabile di infezioni sistemiche, spesso letali, in pazienti immunocompromessi. B. capitatus è un microrganismo ambientale e nell’uomo è presente come commensale nella flora del tratto intestinale e respiratorio e sulla cute.
Una caratteristica peculiare dei miceti patogeni è il dimorfismo. Molti dei miceti di importanza medica esibiscono due diverse morfologie: lievitiforme unicellulare e miceliale pluricellulare. Nei campioni patologici, B. capitatus è stato isolato in entrambe le forme: piccole cellule lievitiformi e micelio con ife settate ramificate.
Le glutatione transferasi (GSTs), una famiglia di enzimi multifunzionali ampiamente distribuita in natura, sono coinvolte nella detossificazione cellulare sia negli eucarioti che nei procarioti. Al contrario di altre specie eucariotiche, le GSTs nei miceti sono state poco studiate e poco si conosce delle loro proprietà strutturali e funzionali.
B. capitatus, isolato da un campione di sangue nella forma lievitiforme, è stato coltivato in vitro nelle due morfologie e per ognuna si è proceduto all’estrazione della frazione citosolica per la purificazione di eventuali forme di GSTs.
Per ogni morfologia è stata purificata una GST mediante due passaggi cromatografici.
Il confronto tra i risultati ottenuti per le due isoforme non ha mostrato significative differenze nella espressione e nell’attività enzimatica indicando che questa GST non è influenzata dalle condizioni ambientali di crescita
Distribution of glutathione transferases in Gram-positive bacteria and Archaea
No full textGlutathione 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. We also performed an analysis on 81 complete genomes of the Archaea domain. Eleven hits were found in the Halobacteriaceae family of the Euryarchaeota phylum and only one in the Crenarchaeota phylum.
A comparison of the identified sequences with well-characterized GSTs belonging to both Gram- negative and eukaryotic GSTs sheds light on their putative function and the evolutionary relationships within the large GST superfamily.
This analysis suggests that the identified sequences mainly cluster in the new Xi class, while Beta class GSTs, widely distributed in Gram-negative bacteria, are under-represented in Gram-positive bacteria and absent in Archaea
Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and neurodegenerative diseases
Full text linkAbstractGlutathione 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. Moreover several GST polymorphisms, ranging from null phenotypes to point mutations, were detected in members of the family and found to correlate with the onset of neuro-degenerative diseases. In the last decades, a great deal of research aimed at clarifying the role played by GSTs in drug resistance, at developing inhibitors to counteract this activity but also at exploiting GSTs for prodrugs specific activation in cancer cells. Here we summarize some of the most important achievements reached in this lively area of research.</jats:p
Compliance therapy with anti-inflammatory antiasthmatic drugs: inhaled corticosteroids and leukotryene receptor antagonists.
No full textA novel amphibian Pi-class glutathione transferase isoenzyme from Xenopus laevis: importance of phenylalanine 111 in the H-site
No full textScreening of a liver tumour cDNA library from Xenopus laevis resulted in the isolation of a full-length cDNA clone encoding a novel Pi-class amphibian glutathione transferase (GST) isoenzyme (designated as XlGSTP1-1). The gene encodes a protein of 212 amino acids with a calculated molecular mass of 24428 Da. The product of the gene has been overexpressed in Escherichia coli and characterized. XlGSTP1-1 has one of the highest specific activities towards 1-chloro-2,4-dinitrobenzene (1310 micromol/min per mg of protein) obtained with any GST. A notable feature of XlGSTP1-1 is the presence in the H-site of Phe(111) and Pro(208) in place of tyrosine and glycine residues respectively, present in other mammalian Pi-class GSTs. Site-directed mutagenesis indicate that Phe(111) is involved in substrate specificity of XlGSTP1-1. We provide evidence showing that XlGSTP1-1 is present only in the embryo and its expression might be associated with cellular proliferation
Evolutionarily conserved structural motifs in bacterial GST (glutathione S-transferase) are involved in protein folding and stability.
No full textThe 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. By contrast with other GSTs, PmGST B1-1 displays distinct hydrogen bond interactions in the N-capping box. In mammalian GSTs these structural elements are critical for protein folding and stability. To investigate the role played by these two motifs in a distantly related organism on the evolutionary scale, site-directed mutagenesis was used to generate several mutants of both motifs in PmGST B1-1. All mutants were efficiently overexpressed and purified, but they were quite unstable, although at different levels, indicating that protein folding was significantly destabilized. The analysis of the T152A and D155G variants indicated that the N-capping box motif plays an important role in the stability and correct folding of the enzyme. The analysis of F151A and A156G mutants revealed that the hydrophobic staple motif influences the structural maintenance of the protein and is implicated in the folding process of PmGST B1-1. Finally, the replacement of Thr152 and Asp155, as well as Phe151 and Ala156 residues influences the catalytic efficiency of the enzyme
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