Unique structural features in a deep-sea CYP51 relate to high pressure adaptation.

Cytochromes P450 (CYP) form one of the largest enzyme superfamilies on Earth, with similar structural fold but biological functions varying from synthesis of physiologically essential compounds to metabolism of myriad xenobiotics. Here we determined the crystal structures of and human sterol 14α-demethylases (CYP51s). Both structures reveal elements that imply elevated conformational flexibility, uncovering molecular basis for faster catalytic rates, lower substrate selectivity, and resistance to inhibition.

Cytochromes b5 Occurrence in Viruses Belonging to the Order Megavirales.

Cytochrome b5 is a small electron transport protein that is found in animals, plants, fungi and photosynthetic proteobacteria where it plays key metabolic roles in energy production, lipid and sterol biosynthesis and cytochrome P450 biochemistry. Previously it was shown that a gene encoding a soluble and functional cytochrome b5 protein was encoded in the large double stranded DNA virus OtV2 that infects the unicellular marine green alga , the smallest free-living eukaryote described to-date. This single gene represented a unique finding in the virosphere.

Structural modeling of cytochrome P450 51 from a deep-sea fish points to a novel structural feature in other CYP51s.

Cytochromes P450 (CYP), enzymes involved in the metabolism of endogenous and xenobiotic substrates, provide an excellent model system to study how membrane proteins with unique functions have catalytically adapted through evolution. Molecular adaptation of deep-sea proteins to high hydrostatic pressure remains poorly understood. Herein, we have characterized recombinant cytochrome P450 sterol 14α-demethylase (CYP51), an essential enzyme of cholesterol biosynthesis, from an abyssal fish species, Coryphaenoides armatus.

Characterization of a Virally Encoded Flavodoxin That Can Drive Bacterial Cytochrome P450 Monooxygenase Activity.

Flavodoxins are small electron transport proteins that are involved in a myriad of photosynthetic and non-photosynthetic metabolic pathways in Bacteria (including cyanobacteria), Archaea and some algae. The sequenced genome of 0305φ8-36, a large bacteriophage that infects the soil bacterium , was predicted to encode a putative flavodoxin redox protein. Here we confirm that 0305φ8-36 phage encodes a FMN-containing flavodoxin polypeptide and we report the expression, purification and enzymatic characterization of the recombinant protein.

Metabolic arsenal of giant viruses: Host hijack or self-use?

Viruses generally are defined as lacking the fundamental properties of living organisms in that they do not harbor an energy metabolism system or protein synthesis machinery. However, the discovery of giant viruses of amoeba has fundamentally challenged this view because of their exceptional genome properties, particle sizes and encoding of the enzyme machinery for some steps of protein synthesis. Although giant viruses are not able to replicate autonomously and still require a host for their multiplication, numerous metabolic genes involved in energy production have been recently detected in giant virus genomes from many environments.

Orphan cytochrome P450 20a1 CRISPR/Cas9 mutants and neurobehavioral phenotypes in zebrafish.

Orphan cytochrome P450 (CYP) enzymes are those for which biological substrates and function(s) are unknown. Cytochrome P450 20A1 (CYP20A1) is the last human orphan P450 enzyme, and orthologs occur as single genes in every vertebrate genome sequenced to date. The occurrence of high levels of CYP20A1 transcripts in human substantia nigra and hippocampus and abundant maternal transcripts in zebrafish eggs strongly suggest roles both in the brain and during early embryonic development.

Developmental exposure to non-dioxin-like polychlorinated biphenyls promotes sensory deficits and disrupts dopaminergic and GABAergic signaling in zebrafish.

The most abundant polychlorinated biphenyl (PCB) congeners found in the environment and in humans are neurotoxic. This is of particular concern for early life stages because the exposure of the more vulnerable developing nervous system to neurotoxic chemicals can result in neurobehavioral disorders. In this study, we uncover currently unknown links between PCB target mechanisms and neurobehavioral deficits using zebrafish as a vertebrate model.

Resolving the Rules of Robustness and Resilience in Biology Across Scales.

Why do some biological systems and communities persist while others fail? Robustness, a system's stability, and resilience, the ability to return to a stable state, are key concepts that span multiple disciplines within and outside the biological sciences. Discovering and applying common rules that govern the robustness and resilience of biological systems is a critical step toward creating solutions for species survival in the face of climate change, as well as the for the ever-increasing need for food, health, and energy for human populations. We propose that network theory provides a framework for universal scalable mathematical models to describe robustness and resilience and the relationship between them, and hypothesize that resilience at lower organization levels contribute to robust systems.

Polycyclic aromatic hydrocarbons modulate the activity of Atlantic cod (Gadus morhua) vitamin D receptor paralogs in vitro.

Vitamin D receptor (VDR) mediates the biological function of the steroid hormone calcitriol, which is the metabolically active version of vitamin D. Calcitriol is important for a wide array of physiological functions, including calcium and phosphate homeostasis. In contrast to mammals, which harbor one VDR encoding gene, teleosts possess two orthologous vdr genes encoding Vdr alpha (Vdra) and Vdr beta (Vdrb).

The chemical defensome of five model teleost fish.

How an organism copes with chemicals is largely determined by the genes and proteins that collectively function to defend against, detoxify and eliminate chemical stressors. This integrative network includes receptors and transcription factors, biotransformation enzymes, transporters, antioxidants, and metal- and heat-responsive genes, and is collectively known as the chemical defensome. Teleost fish is the largest group of vertebrate species and can provide valuable insights into the evolution and functional diversity of defensome genes.

Concerning P450 Evolution: Structural Analyses Support Bacterial Origin of Sterol 14α-Demethylases.

Sterol biosynthesis, primarily associated with eukaryotic kingdoms of life, occurs as an abbreviated pathway in the bacterium Methylococcus capsulatus. Sterol 14α-demethylation is an essential step in this pathway and is catalyzed by cytochrome P450 51 (CYP51). In M.

Remote wireless vital signs monitoring on the ward for early detection of deteriorating patients: A case series.

Introduction: Remote wireless monitoring is a new technology that allows the continuous recording of ward patients' vital signs, supporting nurses by measuring vital signs frequently and accurately. A case series is presented to illustrate how these systems might contribute to improved patient surveillance.

Methods And Results: Five hospitals in three European countries installed a remote wireless vital signs monitoring system on medical or surgical wards.

CRISPR-Cas9-Mutated Pregnane X Receptor (pxr) Retains Pregnenolone-induced Expression of cyp3a65 in Zebrafish (Danio rerio) Larvae.

Pregnane X receptor (PXR; NR1I2) is a nuclear receptor that regulates transcriptional responses to drug or xenobiotic exposure, including induction of CYP3A transcription, in many vertebrate species. PXR is activated by a wide range of ligands that differ across species, making functional studies on its role in the chemical defensome most relevant when approached in a species-specific manner. Knockout studies in mammals have shown a requirement for PXR in ligand-dependent activation of CYP3A expression or reporter gene activity.

On the occurrence of cytochrome P450 in viruses.

Genes encoding cytochrome P450 (CYP; P450) enzymes occur widely in the Archaea, Bacteria, and Eukarya, where they play important roles in metabolism of endogenous regulatory molecules and exogenous chemicals. We now report that genes for multiple and unique P450s occur commonly in giant viruses in the , , and other families in the proposed order Megavirales. P450 genes were also identified in a herpesvirus () and a phage ( phage Adler).

Developmental Regulation of Nuclear Factor Erythroid-2 Related Factors (nrfs) by AHR1b in Zebrafish (Danio rerio).

Interactions between regulatory pathways allow organisms to adapt to their environment and respond to stress. One interaction that has been recently identified occurs between the aryl hydrocarbon receptor (AHR) and the nuclear factor erythroid-2 related factor (NRF) family. Each transcription factor regulates numerous downstream genes involved in the cellular response to toxicants and oxidative stress; they are also implicated in normal developmental pathways.

The stories of women who are transferred due to threat of preterm birth.

Background: Women at risk of preterm birth before 32 weeks gestation are routinely transferred to facilitate birth at a hospital that has Neonatal Intensive Care. The clinical outcomes of being 'in-born" improves newborn and neonatal outcomes is well documented. However little is known about the women's experiences when such a complication occurs.