Article
Biophysics
Kevin F. dos Santos, Elsa M. Materon, Osvaldo N. Oliveira Jr
Summary: This study investigated the influence of cytochrome P450 3A4 (CYP3A4) on the interaction between the drug doxorubicin (DOX) and cell membranes. The results showed that the lipid composition plays a crucial role in this interaction, and that the presence of CYP3A4 significantly reduces the effect of DOX on the cell membranes. These findings support the idea that CYP3A4 is involved in drug resistance and suggest potential strategies to enhance the efficacy of chemotherapy.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Petar M. Mitrasinovic
Summary: The study revealed that chrysin has the largest inhibitory effect on CYP3A4, while quercetin and flavopiridol serve as representative examples of structurally different flavonoids. The inhibition parameters for these compounds were evaluated using the calibrated QM/MM strategy, aiding in quantitatively understanding the functional behavior of the whole flavonoid family. Additionally, a kinetic threshold for further assessment of the time-dependent inhibition of CYP3A4 by flavonoids was explored.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Physical
Nico D. Fessner, Christopher Grimm, Matic Srdic, Hansjoerg Weber, Wolfgang Kroutil, Ulrich Schwaneberg, Anton Glieder
Summary: This study explores the synthetic potential of human P450 3A4 in diversifying natural product classes, resulting in the identification of 31 authentic human metabolites. With efficient expression levels in P. pastoris, this biocatalyst shows promising results for modifying natural products in a one-step fashion.
Article
Pharmacology & Pharmacy
V. H. Amstutz, A. Cengo, D. T. H. M. Sijm, M. F. Vrolijk
Summary: Per- and polyfluomalkyl substances (PFASs) have been associated with hepatotoxicity, and their interaction with cytochrome P450 (CYP) has been proposed as a potential mechanism. This study explored the inhibitory potential of thirteen PFASs on four CYPs, revealing that most PFASs can inhibit CYP activity. The inhibition mechanism varied among different CYP isoenzymes. Some PFASs also induced increased CYP activity. These findings suggest that multiple novel PFASs may interfere with drug metabolism by affecting CYPs.
Article
Chemistry, Medicinal
Shiwei Lu, Feng Zhang, Jiahao Gong, Jian Huang, Guanghao Zhu, Yitian Zhao, Qi Jia, Yiming Li, Bo Li, Kaixian Chen, Weiliang Zhu, Guangbo Ge
Summary: This study discovered potent and orally active hCYP3A4 inhibitors from chalcone derivatives and tested their effects on hCYP3A4 in vitro and in vivo. The isoquinoline chalcones were found to have excellent anti-hCYP3A4 effects after screening and optimization. SAR studies revealed the structural requirements for enhancing the anti-CYP3A4 effect. A lead compound, C6, was identified as the most potent hCYP3A4 inhibitor and showed good metabolic stability and safety profiles. In vivo tests demonstrated the efficacy of C6 in increasing drug exposure and prolonging drug half-life. Overall, this study offers valuable insights into developing novel CYP3A4 inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Analytical
Michael Riffle, Michael R. Hoopmann, Daniel Jaschob, Guo Zhong, Robert L. Moritz, Michael J. MacCoss, Trisha N. Davis, Nina Isoherranen, Alex Zelter
Summary: The study introduces Magnum and Limelight, an algorithm and software package for the identification and visualization of xenobiotic-protein adducts. Through validation and application, the methods and software enable accurate identification of xenobiotic-protein adducts and fill the gap in comprehensive data visualization tools in the field of open-mass searching.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Idowu Kehinde, Rene Khan, Manimbulu Nlooto, Michelle Gordon
Summary: This study investigated the effects of four plant-derived compounds on drug-metabolizing proteins in HepG2 and HEK293 cells, finding that these compounds may enhance drug bioavailability at certain concentrations.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Shosei Kano, Hiroshi Takahashi
Summary: Studies have shown that cholesterol plays a role in the drug metabolism process mediated by cytochrome P450 (CYP). The lower concentration of cholesterol in the endoplasmic reticulum (ER) membrane compared to other organelle membranes allows CYP-substrate drugs to enter the hydrophobic region of the ER membrane more easily, resulting in efficient drug metabolism.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2022)
Article
Immunology
Kristina Jonsson-Schmunk, Romi Ghose, Maria A. Croyle
Summary: The study discovered that infection and vaccines can have an impact on the activity of the CYP3A4 enzyme in liver cells, which may lead to impaired drug metabolism. Therefore, it is essential to evaluate the effects of new vaccines and emerging pathogens on metabolic enzymes in the clinical assessment of global pathogen vaccines.
EXPERT REVIEW OF VACCINES
(2021)
Article
Biochemistry & Molecular Biology
Yasuhiro Yonezuka, Hiroki Kuwada, Hiromasa Imaishi
Summary: This study demonstrated the effectiveness of the P450 inhibition assay in a mouse model of DILI, suggesting its potential for diagnosing liver diseases such as acute DILI.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Plant Sciences
Saneesh Kumar, Patrick J. Bouic, Bernd Rosenkranz
Summary: The study evaluated the effects of Withania somnifera root extracts on cytochromes P450, finding that they may cause clinically significant herb-drug interactions by affecting the metabolism pathway of drugs such as rifampicin.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Philip Hartz, Tobias Fehlmann, Gudrun Wagenpfeil, Marcus Michael Unger, Rita Bernhardt
Summary: Genetic and environmental factors contribute to the development of Parkinson's disease, with only limited understanding of the underlying mechanisms. Cytochromes P450 (P450s) play a role in the metabolism of toxic compounds and physiological processes, potentially influencing Parkinson's disease. However, only SNPs in CYP2D6 and CYP2E1 have been associated with Parkinson's disease susceptibility.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Harpreet Kaur, Drew Seeger, Svetlana Golovko, Mikhail Golovko, Colin Kelly Combs
Summary: Alzheimer's disease is a neurodegenerative disease characterized by progressive cognitive impairment, with studies suggesting the involvement of liver cholesterol and bile acid metabolism in its pathophysiology. Experimental results from two different AD mouse lines indicate fundamental deficiencies in liver cholesterol metabolism and bile acid synthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Xueyao Jiang, Jing Wu, Boyu Tan, Sulan Yan, Nan Deng, Hongyan Wei
Summary: This study found that chronic unpredictable mild stress (CUMS)-induced depression alters the pharmacokinetics of clopidogrel, and the changes in CYP450 activity and expression in the livers of depressed rats may contribute to the disturbance of clopidogrel pharmacokinetics.
Article
Biochemistry & Molecular Biology
Yuri D. Ivanov, Amir Taldaev, Andrey V. Lisitsa, Elena A. Ponomarenko, Alexander I. Archakov
Summary: The study predicted the three-dimensional structures of CYP102A1/WT proteins and their mutant forms using AlphaFold programs. The structures of monomers in the homodimer were found to be consistent with experimental structures, while the predicted structures of isolated monomers were different. Significant differences were observed in the structure of monomers compared to homodimers for the mutant forms. Comparative analysis showed a correlation between the electron transfer rate constants and the distances between prosthetic groups.
Article
Chemistry, Multidisciplinary
Katriann Arja, Robert Selegard, Marketa Paloncyova, Mathieu Linares, Mikael Lindgren, Patrick Norman, Daniel Aili, K. Peter R. Nilsson
Summary: This study reports on the chiro-optical properties and architectural arrangement of optoelectronic materials generated through self-assembly of oligothiophene-porphyrin derivatives and synthetic peptides. The materials exhibit a three-dimensional ordered helical structure and optical activity, making them promising for bioelectronic applications.
Article
Chemistry, Physical
Nikolas P. Benetis, Marketa Paloncyova, Stefan Knippenberg
Summary: The study investigates the embedding of caffeate methyl ester, luteolin, quercetin, o-phenanthroline, and neocuproine in a liquid disordered lipid bilayer through atomistic calculations, explaining their location and orientation as bio-active antioxidants. The phenanthrolines associate strongly with the lipid tail region, while the other compounds are found among the head groups. The simulations show conformational changes of the flavonoids. The study analyzes the influence of the anisotropic environment on the compounds' optical properties using a hybrid quantum mechanics-molecular mechanics scheme, and highlights the importance of mapping molecular interactions in model membranes for biomedical applications relating to different lipid environments.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Chemistry, Physical
Marketa Paloncyova, Martin Srejber, Petra Cechova, Petra Kuhrova, Filip Zaoral, Michal Otyepka
Summary: RNA-based therapies have shown promise in various applications. Encapsulation of RNA into lipid nanoparticles allows for safe and targeted delivery. Simulations of pH-sensitive RNA-carrying nanoparticles reveal their self-assembly process and internal structure, providing insights into their composition and potential interactions for improving RNA-based medicine.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Chemistry, Multidisciplinary
Michal Langer, Lukas Zdrazil, Miroslav Medved, Michal Otyepka
Summary: The establishment of structure-photoluminescence (PL) relationships in carbon dots (CDs) is still a challenge. The core, surface, and molecular states are the main sources of PL, but their interaction and effects on each other are not well understood. By performing TD-DFT calculations, researchers found that different structural arrangements support the communication between PL centers. This study provides insights for designing CDs with desired surface/core characteristics.
Article
Chemistry, Medicinal
Petra Kuhrova, Vojtech Mlynsky, Michal Otyepka, Jiri Sponer, Pavel Banas
Summary: RNA molecules play a key role in biochemical processes and interact closely with ions and water molecules. Double-stranded RNA is important for RNA folding and the design of RNA-based nanostructures. This study used molecular dynamics simulations to investigate the effects of ion concentrations and solvation box size on A-RNA structure.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Medicine, Research & Experimental
Martin Balouch, Katerina Storchmannova, Frantisek Stepanek, Karel Berka
Summary: Encapsulation into liposomes is a formulation strategy that improves drug efficacy and reduces side effects. However, some drugs are not suitable for liposomal formulations due to their properties. Several options for solving this issue include changing the lipid bilayer composition, adding permeability enhancers, or modifying the chemical structure of the drug.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Aliaksei Chareshneu, Adam Midlik, Crina-Maria Ionescu, Alexander Rose, Vladimir Horsky, Alessio Cantara, Radka Svobodova, Karel Berka, David Sehnal
Summary: Segmentation is important for interpreting imaging data in a biological context. Mol*VS is a web-based tool that allows interactive visualization of 3D volume segmentations, supporting cellular imaging data and biological annotations.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Ondrej Schindler, Karel Berka, Alessio Cantara, Ales Krenek, Dominik Tichy, Tomas Racek, Radka Svobodova
Summary: The AlphaFold2 prediction algorithm has allowed for the exploration of protein structural space on a large scale. A web application called alpha Charges has been introduced for the quick calculation of partial atomic charges for protein structures from AlphaFoldDB.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Aby Cheruvathoor Poulose, Miroslav Medved, Vasudeva Rao Bakuru, Akashdeep Sharma, Deepika Singh, Suresh Babu Kalidindi, Hugo Bares, Michal Otyepka, Kolleboyina Jayaramulu, Aristides Bakandritsos, Radek Zboril
Summary: This study presents a reusable graphene catalyst that can convert glycerol, produced from biomass fermentation, to high-value chemicals at room temperature without solvents. The catalyst shows excellent activity and selectivity for glycerol conversion to solketal, and it can also convert oils to biodiesel.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Jan Chasak, Lauren Oorts, Milan Dak, Veronika Slachtova, Vaclav Bazgier, Karel Berka, Linda De Vooght, Natalia Smiejkowska, Kevin Van Calster, Laurence Van Moll, Davie Cappoen, Paul Cos, Lucie Brulikova
Summary: This study aims to develop new antimycobacterial agents against drug-resistant tuberculosis by inhibiting mycobacterial ATP synthase. Squaric acid analogues were synthesized and explored, with phenyl-substituted compounds showing the best inhibition effect. Deeper insights into their mechanisms of action were gained, and a single point mutation in the atpB gene responsible for ATP synthase subunit a was validated as the molecular basis of resistance to squaramides. The study also highlights the potential synergy between squaramides and clofazimine, providing a promising avenue for enhancing the effectiveness of existing treatments.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Remi Coulon, Barbora Papouskova, Elmira Mohammadi, Michal Otyepka, Sreekar Wunnava, Jiri Sponer, Judit E. Sponer
Summary: 3',5'-Cyclic nucleotides play a fundamental role in modern biochemical processes and may have played a central role in the origin of early terrestrial life. A formamide-based systems chemistry could explain their availability on early Earth, as demonstrated by the formation of 3',5'-cyclic nucleotides in liquid formamide environments at elevated temperatures.
Article
Chemistry, Physical
Rabindranath Lo, Martin Pykal, Andreas Schneemann, Radek Zboril, Roland A. Fischer, Kolleboyina Jayaramulu, Michal Otyepka
Summary: Covalent hybrids of graphene and metal-organic frameworks (MOFs) have great potential in various technologies, especially catalysis and energy applications, due to their combination of conductivity and porosity. The formation of an amide bond between carboxylate-functionalized graphene acid (GA) and amine-functionalized UiO-66-NH2 MOF is an efficient strategy for creating such hybrids. This study used density functional theory (DFT) calculations to elucidate the mechanism of amide bond formation between GA and UiO-66-NH2, highlighting the crucial role of zirconium within UiO-66 as a catalyst. Insight into the binding interactions between graphene derivatives and MOFs can lead to tailored synthesis strategies for these nanocomposite materials.
JOURNAL OF PHYSICAL CHEMISTRY C
(2023)
Article
Chemistry, Multidisciplinary
Marina Gonzalez-Sanchez, Mariia J. Mayoral, Violeta Vazquez-Gonzalez, Marketa Paloncyova, Irene Sancho-Casado, Fatima Aparicio, Alberto de Juan, Giovanna Longhi, Patrick Norman, Mathieu Linares, David Gonzalez-Rodriguez
Summary: Self-assembled nanotubes with distinct internal arrangements and properties are achieved through different supramolecular scenarios prior to polymerization, driven by chelate cooperativity and self-recognition motifs at the edges. The chosen supramolecular pathway for structurally related molecules with complementary nucleobases is determined by their propensity for specific cyclic structures through Watson-Crick pairing. These findings provide insight into the unpredictability and experimental evaluation of self-assembly pathways, as well as the design of functional nanomaterials with controlled helicity and chiroptical properties.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Anna Spackova, Ondrej Vavra, Tomas Racek, Vaclav Bazgier, David Sehnal, Jiri Damborsky, Radka Svobodova, David Bednar, Karel Berka
Summary: ChannelsDB 2.0 is an updated database that provides structural information about the position, geometry, and physicochemical properties of protein channels and pores. It incorporates data calculated by CAVER and MOLE tools, as well as additional information from AlphaFill database, resulting in significantly expanded channel annotations. The database stores information such as geometrical features and physico-chemical properties based on channel-lining amino acids, and is interlinked with UniProt mutation annotation data. ChannelsDB 2.0 serves as an important resource for in-depth analysis of the role of biomacromolecular tunnels and pores.
NUCLEIC ACIDS RESEARCH
(2023)
