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Escherichia coli --- Escherichia coli --- Enzyme activity --- Enzyme activity --- Cytochrome P450 --- Cytochrome P450 --- recombination --- recombination --- culture media --- culture media

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Genetic variations may change the structure and function of individual proteins as well as affect their interactions with other proteins and thereby impact metabolic processes dependent on protein-protein interactions. For example, cytochrome P450 proteins, which metabolize a vast array of drugs, steroids and other xenobiotics, are dependent on interactions with redox and allosteric partner proteins for their localization, stability, (catalytic) function and metabolic diversity (reactions). Genetic variations may impact such interactions by changing the splicing and/or amino acid sequence which in turn may impact protein topology, localization, post translational modifications and three dimensional structure. More generally, research on single gene defects and their role in disease, as well as recent large scale sequencing studies suggest that a large number of genetic variations may contribute to disease not only by affecting gene function or expression but also by modulating complex protein interaction networks.The aim of this research topic is to bring together researchers working in the area of drug, steroid and xenobiotic metabolism who are studying protein-protein interactions, to describe their recent advances in the field. We are aiming for a comprehensive analysis of the subject from different approaches including genetics, proteomics, transcriptomics, structural biology, biochemistry and pharmacology. Of particular interest are papers dealing with translational research describing the role of novel genetic variations altering protein-protein interaction. Authors may submit original articles, reviews and opinion or hypothesis papers dealing with the role of protein-protein interactions in health and disease.

POR --- Pharmacogenetics --- UGT --- Biocatalysis --- UDP-glucuronosyltransferase --- Cytochrome P450 --- Drug metabolism --- Membrane-associated progesterone receptor --- PXR --- Steroids

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Genetic variations may change the structure and function of individual proteins as well as affect their interactions with other proteins and thereby impact metabolic processes dependent on protein-protein interactions. For example, cytochrome P450 proteins, which metabolize a vast array of drugs, steroids and other xenobiotics, are dependent on interactions with redox and allosteric partner proteins for their localization, stability, (catalytic) function and metabolic diversity (reactions). Genetic variations may impact such interactions by changing the splicing and/or amino acid sequence which in turn may impact protein topology, localization, post translational modifications and three dimensional structure. More generally, research on single gene defects and their role in disease, as well as recent large scale sequencing studies suggest that a large number of genetic variations may contribute to disease not only by affecting gene function or expression but also by modulating complex protein interaction networks.The aim of this research topic is to bring together researchers working in the area of drug, steroid and xenobiotic metabolism who are studying protein-protein interactions, to describe their recent advances in the field. We are aiming for a comprehensive analysis of the subject from different approaches including genetics, proteomics, transcriptomics, structural biology, biochemistry and pharmacology. Of particular interest are papers dealing with translational research describing the role of novel genetic variations altering protein-protein interaction. Authors may submit original articles, reviews and opinion or hypothesis papers dealing with the role of protein-protein interactions in health and disease.

POR --- Pharmacogenetics --- UGT --- Biocatalysis --- UDP-glucuronosyltransferase --- Cytochrome P450 --- Drug metabolism --- Membrane-associated progesterone receptor --- PXR --- Steroids

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This book, "Cytochromes P450: Drug Metabolism, Bioactivation and Biodiversity", presents five papers on human cytochrome P450 (CYP) and P450 reductase, three reviews on the role of CYPs in humans and their use as biomarkers, six papers on CYPs in microorganisms, and one study on CYP in insects. The first paper reports the in silico modeling of human CYP3A4 access channels. The second uses structural methods to explain the mechanism-based inactivation of CYP3A4 by mibefradil, 6,7-dihydroxy-bergamottin, and azamulin. The third article compares electron transfer in CYP2C9 and CYP2C19 using structural and biochemical methods, and the fourth uses kinetic methods to study electron transfer to CYP2C8 allelic mutants. The fifth article characterizes electron transfer between the reductase and CYP using in silico and in vitro methods, focusing on the conformations of the reductase. Then, two reviews describe clinical implications in cardiology and oncology and the role of fatty acid metabolism in cardiology and skin diseases. The second review is on the potential use of circulating extracellular vesicles as biomarkers. Five papers analyze the CYPomes of diverse microorganisms: the Bacillus genus, Mycobacteria, the fungi Tremellomycetes, Cyanobacteria, and Streptomyces. The sixth focuses on a specific Mycobacterium CYP, CYP128, and its importance in M. tuberculosis. The subject of the last paper is CYP in Sogatella furcifera, a plant pest, and its resistance to the insecticide sulfoxaflor.

Research & information: general --- Antibiotics --- Bacillus --- biosynthetic gene clusters --- comparative analysis --- cytochrome P450 monooxygenase --- Mycobacterium --- P450 diversity percentage --- P450 profiling --- secondary metabolites --- NADPH-cytochrome P450 reductase (CPR) --- microsomal cytochrome P450 (CYP) --- Cytochrome b5 (CYB5) --- protein dynamics --- electron-transfer (ET) --- protein–protein interaction --- cytochromes P450 --- CYP3A4 --- active site access channels --- cavities boundaries --- minimal cost paths --- CYP139A1 --- genome data mining --- host metabolism --- Mycobacterium tuberculosis --- polyketides --- tuberculosis --- cryptococcus --- cryptococcus neoformans --- CYP51 --- fungal pathogens --- genome data-mining --- human pathogens --- CYP diversity analysis --- tremellomycetes --- trichosporon --- mechanism-based inhibitor --- crystal structure --- CYP4 genes --- genetic polymorphisms --- 20-HETE --- fatty acid --- arachidonic acid --- SNPs --- molecular functionality --- metabolism --- lamellar ichthyosis --- Bietti’s crystalline dystrophy --- cytochrome P450 --- isoform --- membrane protein --- protein-membrane interactions --- enzyme substrate specificity --- mutagenesis --- molecular dynamics simulation --- Sogatella furcifera --- sulfoxaflor --- transcriptome --- RNA interference --- CYP2C8 --- polymorphisms --- reactive oxygen species --- paclitaxel --- cytochrome P450 reductase --- electron transfer --- extracellular vesicles --- exosomes --- extrahepatic tissues --- plasma --- circulatory CYPs --- CYP450 --- drug metabolism --- precision Cardio-Oncology --- precision medicine --- systems medicine --- cytochromes P450 monooxygenases --- Cyanobacteria --- gene-cluster diversity percentage --- mathematical formula --- phylogenetic analysis --- Streptomyces --- cytochrome P450 monooxygenases --- terpenes --- P450 blooming --- non-ribosomal peptides --- cytochrome P450 monooxygenenases --- CYP128A1 --- Mycobacterium tuberculosis H37Rv --- molecular dynamic simulations --- azole drugs --- menaquinone --- Antibiotics --- Bacillus --- biosynthetic gene clusters --- comparative analysis --- cytochrome P450 monooxygenase --- Mycobacterium --- P450 diversity percentage --- P450 profiling --- secondary metabolites --- NADPH-cytochrome P450 reductase (CPR) --- microsomal cytochrome P450 (CYP) --- Cytochrome b5 (CYB5) --- protein dynamics --- electron-transfer (ET) --- protein–protein interaction --- cytochromes P450 --- CYP3A4 --- active site access channels --- cavities boundaries --- minimal cost paths --- CYP139A1 --- genome data mining --- host metabolism --- Mycobacterium tuberculosis --- polyketides --- tuberculosis --- cryptococcus --- cryptococcus neoformans --- CYP51 --- fungal pathogens --- genome data-mining --- human pathogens --- CYP diversity analysis --- tremellomycetes --- trichosporon --- mechanism-based inhibitor --- crystal structure --- CYP4 genes --- genetic polymorphisms --- 20-HETE --- fatty acid --- arachidonic acid --- SNPs --- molecular functionality --- metabolism --- lamellar ichthyosis --- Bietti’s crystalline dystrophy --- cytochrome P450 --- isoform --- membrane protein --- protein-membrane interactions --- enzyme substrate specificity --- mutagenesis --- molecular dynamics simulation --- Sogatella furcifera --- sulfoxaflor --- transcriptome --- RNA interference --- CYP2C8 --- polymorphisms --- reactive oxygen species --- paclitaxel --- cytochrome P450 reductase --- electron transfer --- extracellular vesicles --- exosomes --- extrahepatic tissues --- plasma --- circulatory CYPs --- CYP450 --- drug metabolism --- precision Cardio-Oncology --- precision medicine --- systems medicine --- cytochromes P450 monooxygenases --- Cyanobacteria --- gene-cluster diversity percentage --- mathematical formula --- phylogenetic analysis --- Streptomyces --- cytochrome P450 monooxygenases --- terpenes --- P450 blooming --- non-ribosomal peptides --- cytochrome P450 monooxygenenases --- CYP128A1 --- Mycobacterium tuberculosis H37Rv --- molecular dynamic simulations --- azole drugs --- menaquinone

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Science: general issues --- Pharmacology --- Pharmacogenetics --- Pharmacogenomics --- Epigenome --- Polymorphisms --- Personalized Medicine --- Precision medicine --- Precision psychiatry --- Predictive testing --- Gene-based treatment --- P450 --- Pharmacogenetics --- Pharmacogenomics --- Epigenome --- Polymorphisms --- Personalized Medicine --- Precision medicine --- Precision psychiatry --- Predictive testing --- Gene-based treatment --- P450