Characterization of high-H2O2-tolerant bacterial cytochrome P450 CYP105D18: insights into papaverine N-oxidation

The bacterial CYP105 family is involved in secondary metabolite biosynthetic pathways and plays essential roles in the biotransformation of xenobiotics. This study investigates the newly identified H2O2-mediated CYP105D18 from Streptomyces laurentii as the first bacterial CYP for N-oxidation. The catalytic efficiency of CYP105D18 for papaverine N-oxidation was 1.43 s−1 µM −1. The heme oxidation rate (k) was low (<0.3 min−1) in the presence of 200 mM H2O2. This high H2O2 tolerance capacity of CYP105D18 led to higher turnover prior to heme oxidation. Additionally, the high-resolution papaverine complexed structure and substrate-free structure of CYP105D18 were determined. Structural analysis and activity assay results revealed that CYP105D18 had a strong substrate preference for papaverine because of its bendable structure. These findings establish a basis for biotechnological applications of CYP105D18 in the pharmaceutical and medicinal industries.

Prophylaxis of dental caries in children from polluted regions

To be living at the most advanced technological area in history is to exist and face pollution one of the most serious threats to all living things on the planet. There is evidence that anthropogenic and technological pollutions cause a considerable number of health problems and stomatological in particular. This article demonstrates the results gained by administration of vitamin-macro element complex “Calcinova” and sorbent “Enterosgel” in correction of enzymes responsible for biotransformation of xenobiotics in blood serum of children from the polluted areas. It has been established the high efficiency of recommended scheme on caries prophylaxis that is proved by positive biochemical indexes in blood serum of this children observed 30 month after the beginning of the investigation. As a result of the introduced prophylaxis, we have noticed the significant improvement of biochemical indexes in children with tooth decay. The findings reflect a certain rise in activity of enzymes responsible for elimination of xenobiotics such as alcohol-dehydrogenase (ADH) and glutathione-S-transferase (GST) obtained from the blood serum of children from the main group comparing to the control group.

ROLE OF GSTM AND GSTT POLYMORPHIC GENES IN ONCOGENESIS AND THE ONSET OF HEMATOLOGIC NEOPLASMS

Throughout life, a person is exposed to various xenobiotics, one of the biological effects of which is the genotoxic effect, leading to the occurrence of oncogenic mutations. Mutagenic and promutagenic substances can be detoxified with the corresponding xenobiotic biotransformation enzymes, however, if the enzymatic activity of the latter changes, the neutralization of the mutagens occurs at a slower pace. The review discusses the polymorphic genes of enzymes of the second phase of the biotransformation of xenobiotics of the GSTS family and presents modern literature data on the role of GSTM and GSTT in oncogenesis and the development of hemoblastoses. The search of scientific literature was carried out using the PubMed and СyberLeninka databases.

Microbial genetic potential for xenobiotic metabolism increases with depth during biofiltration

Microbial genetic potential for the biotransformation of xenobiotics and antibiotic resistance increases with depth during biofiltration.

In situ proteolysis of an N-terminal His tag with thrombin improves the diffraction quality of human aldo-keto reductase 1C3 crystals

Human aldo-keto reductase 1C3 (AKR1C3) stereospecifically reduces steroids and prostaglandins and is involved in the biotransformation of xenobiotics. Its role in various cancers makes it a potential therapeutic target for the development of inhibitors. Recombinant AKR1C3 with a thrombin-cleavable N-terminal His6 tag was expressed from a pET-28(+) vector for structural studies of enzyme–inhibitor complexes. A modified in situ proteolysis approach was applied to specifically remove the His tag by thrombin cleavage during crystallization screening trials. This improved the morphology and diffraction quality of the crystals and allowed the acquisition of high-resolution diffraction data and structure solution. This approach may be generally applicable to other proteins expressed using the pET-28(+) vector.

Glutathionylation: a regulatory role of glutathione in physiological processes

Glutathione (γ-glutamyl-cysteinyl-glycine) is an intracellular thiol molecule and a potent antioxidant that participates in the toxic metabolism phase II biotransformation of xenobiotics. It can bind to a variety of proteins in a process known as glutathionylation. Protein glutathionylation is now recognised as one of important posttranslational regulatory mechanisms in cell and tissue physiology. Direct and indirect regulatory roles in physiological processes include glutathionylation of major transcriptional factors, eicosanoids, cytokines, and nitric oxide (NO). This review looks into these regulatory mechanisms through examples of glutathione regulation in apoptosis, vascularisation, metabolic processes, mitochondrial integrity, immune system, and neural physiology. The focus is on the physiological roles of glutathione beyond biotransformational metabolism.