Article
Biochemistry & Molecular Biology
Remigio Usai, Daniel Kaluka, Sheng Cai, Daniel S. Sem, James R. Kincaid
Summary: A new method using heterologous expression of 13C-labeled P450cam was developed to define and refine the solution phase active site structure in cytochrome P450cam.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Manuel Sellner, Andre Fischer, Charleen G. Don, Martin Smiesko
Summary: Research using molecular dynamics simulations and protein-protein docking revealed the mechanism of conformational changes between cytochrome P450 enzymes and cytochrome P450 reductase, as well as proposed new conformational transition mechanisms and structural mechanisms for susceptibility to redox states.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Tugce Sakalli, Nur Basak Surmeli
Summary: By studying the variant DM CYP119 of acidothermophilic P450, it was found to have higher stability towards organic peroxides and higher peroxidation activity for non-natural substrates compared to wild-type CYP119. It also showed higher affinity for progesterone and other bioactive potential substrates, indicating its wide range of potential applications in the pharmaceutical and chemical industry.
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
(2022)
Article
Chemistry, Physical
Lev Levintov, Harish Vashisth
Summary: RNA molecules, including viral RNA like TAR RNA from HIV-1, undergo conformational changes in response to environmental stimuli. When TAR RNA binds to ligands, its structure becomes significantly more stable with reduced fluctuations in helices. Unliganded TAR structures exhibit conformational dynamics that lead to the formation of binding pockets for ligands.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Review
Chemistry, Multidisciplinary
Iori Morita, Takahiro Mori, Ikuro Abe
Summary: Teleocidins are potent protein kinase C activators with a unique indole-fused nine-membered lactam structure synthesized through a multi-step biosynthetic process involving NRPS, cytochrome P450 oxidase, prenyltransferase, and C-methyltransferase. Recent research has focused on elucidating the molecular basis for the challenging P450-catalyzed intramolecular C-N bond formation, leading to the generation of indolactam scaffold, as well as the production of unnatural and novel molecular scaffolds through precursor-directed biosynthesis using promiscuous P450 enzymes.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Pharmacology & Pharmacy
Chiemela S. S. Odoemelam, Elena Hunter, Zeeshan Ahmad, Caroline Lynn Kamerlin, Samuel White, Philippe B. B. Wilson
Summary: This study investigated the interactions of selected flavonoids with cytochrome P450 enzymes and found that isorhamnetin and pedalitin had the strongest binding energies. These flavonoids may serve as potential precursors for natural product-derived therapies.
CURRENT PHARMACEUTICAL DESIGN
(2022)
Article
Chemistry, Physical
F. Peter Guengerich, Stella A. Child, Ian R. Barckhausen, Margo H. Goldfarb
Summary: The bacterial cytochrome P450(cam) binds its substrate camphor through an induced-fit mechanism, where the enzyme changes conformation after binding the substrate. This behavior is different from other P450 enzymes that utilize a conformational selection process for substrate recognition. The accessory protein putidaredoxin has no effect on substrate binding, indicating a unique mechanism for substrate recognition by P450(cam).
Article
Health Care Sciences & Services
Masaki Kumondai, Evelyn Gutierrez Rico, Eiji Hishinuma, Yuya Nakanishi, Shuki Yamazaki, Akiko Ueda, Sakae Saito, Shu Tadaka, Kengo Kinoshita, Daisuke Saigusa, Tomoki Nakayoshi, Akifumi Oda, Noriyasu Hirasawa, Masahiro Hiratsuka
Summary: Functional characterization of 21 novel CYP1A2 variants revealed that most variants exhibited decreased or no enzymatic activity, possibly due to potential structural alterations. Some variants did not exhibit quantifiable enzymatic activity, and further 3D docking analyses helped to understand the mechanisms underlying protein function impairment caused by mutations.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Christopher S. Campomizzi, George E. Ghanatios, D. Fernando Estrada
Summary: Cytochromes P450 are versatile enzymes involved in endogenous and exogenous metabolism, undergoing structural changes related to function. This study demonstrates the utility of fluorine (19F)-NMR spectroscopy in monitoring structural changes in CYP121A1, revealing insights into its role in substrate recognition and mechanistic details of this essential enzyme from Mycobacterium tuberculosis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Health Care Sciences & Services
Masaki Kumondai, Akio Ito, Evelyn Marie Gutierrez Rico, Eiji Hishinuma, Akiko Ueda, Sakae Saito, Tomoki Nakayoshi, Akifumi Oda, Shu Tadaka, Kengo Kinoshita, Masamitsu Maekawa, Nariyasu Mano, Noriyasu Hirasawa, Masahiro Hiratsuka
Summary: This study characterized the functional differences in CYP2C9 variants in Japanese individuals, revealing significantly reduced or null enzymatic activity compared to the wild-type and a strong correlation in catalytic efficiencies between (S)-warfarin and tolbutamide metabolism. The observed perturbation in enzyme activity was evaluated through three-dimensional structural modeling, providing insights to improve personalized medicine, particularly in selecting appropriate warfarin dose based on rare allelic variants of CYP2C9.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Andre Fischer, Martin Smiesko
Summary: This study investigates an allosteric site in Cytochrome P450 enzymes, finding it to be well conserved in the CYP2 family with the exception of CYP2E1, and observing an enlargement of ligand tunnels in certain members that facilitate ligand translocation. The research contributes to understanding ligand access phenomena and aids in estimating the selectivity of metabolic transformations using computational techniques.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Linda Celeste Montemiglio, Elena Gugole, Ida Freda, Cecile Exertier, Lucia D'Auria, Cheng Giuseppe Chen, Alessandro Nicola Nardi, Gabriele Cerutti, Giacomo Parisi, Marco D'Abramo, Carmelinda Savino, Beatrice Vallone
Summary: This study analyzed the role of a cavity in substrate binding to OleP by mutating its volume. The results showed that inserting bulky residues into the cavity affected the binding properties of the enzyme and perturbed the conformational space of the substrate-enzyme complex. The study highlights the importance of this region in OleP substrate binding and suggests the potential to redirect its activity through this region.
Article
Genetics & Heredity
Dean S. S. Rosenthal, Li-Wei Kuo, Sarah L. L. Seagrave, Vikas Soni, Nusrat Islam, Geetanjali Minsky, Lucia Dussan-Cuellar, Brian Ell, Cynthia M. M. Simbulan-Rosenthal, Peter Sykora
Summary: The targets of topical genotoxic agents are basal and stem cells of the skin. However, the genotoxicity of many compounds has not yet been determined and needs to be tested using a relevant skin model. This study designed a new high-throughput assay to detect DNA damage in epidermal stem and basal cells, and confirmed significant genotoxicity of known DNA-damaging agents.
Article
Plant Sciences
Habtamu Ayalew, William Schapaugh, Tri Vuong, Henry T. Nguyen
Summary: This study evaluated soybean genotypes with different maturity groups for seed yield and other traits in various environments, and identified significant loci associated with seed yield through genome-wide association studies. Two stable quantitative trait loci on chromosomes 9 and 17 were found to be strongly associated with seed yield.
Article
Biodiversity Conservation
Takatoshi Wakabayashi, Megumi Nakayama, Yurie Kitano, Masato Homma, Kenji Miura, Hirosato Takikawa, Masaharu Mizutani, Yukihiro Sugimoto
Summary: Parasitic witchweeds (Striga species) are a serious threat to food security in Africa, attacking cereal grains and legumes. The chemicals released from host roots, known as germination stimulants, mainly strigolactones (SLs), were first identified in cotton root exudates over 50 years ago. This discovery of a complete biosynthesis pathway for strigolactones in cotton has the potential to enhance our understanding of SL-mediated rhizosphere interactions and improve cotton's effectiveness as a trap crop.
PLANTS PEOPLE PLANET
(2023)
Article
Multidisciplinary Sciences
Pau Castel, Srisathiyanarayanan Dharmaiah, Matthew J. Sale, Simon Messing, Gabrielle Rizzuto, Antonio Cuevas-Navarro, Alice Cheng, Michael J. Trnka, Anatoly Urisman, Dominic Esposito, Dhirendra K. Simanshu, Frank McCormick
Summary: This study investigated the role of Sin1 as a RAS effector through biochemical and structural methods, revealing that the interaction between Sin1 and RAS is not necessary for the function of mTORC2.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Srivats Venkataramanan, Margaret Gadek, Lorenzo Calviello, Kevin Wilkins, Stephen N. Floor
Summary: DDX3 is a DEAD-box RNA helicase encoded by X- and Y-linked paralogs DDX3X and DDX3Y. DDX3X is ubiquitously expressed and essential for viability, while DDX3Y is male-specific and shows lower expression in somatic tissues. Both paralogs play redundant roles in translation, with DDX3Y able to complement DDX3X in rescuing transcripts sensitive to DDX3X depletion or mutation. The expression differences, rather than differences in protein synthesis, between DDX3X and DDX3Y may underlie the sex-bias of DDX3X-associated diseases.
Article
Biochemistry & Molecular Biology
Nicholas A. Sanchez, Lena M. Kallweit, Michael J. Trnka, Charles L. Clemmer, Bassem Al-Sady
Summary: The study reveals that the reading and writing activities of H3K9me are significantly enhanced in the heterodimer, with higher recognition of H3K9me2 and a striking increased turnover rate for nucleosomal substrates. Cross-linking Mass Spectrometry suggests that differences between the homodimers and the unique activity of the heterodimer may be encoded in altered ground state conformations.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Brian C. Tooker, Sylvie E. Kandel, Hannah M. Work, Jed N. Lampe
Summary: In this study, the function of CYP168A1 from Pseudomonas aeruginosa was characterized, and it was found to have the ability to hydroxylate fatty acids, particularly arachidonic acid. The enzyme has a large, expansive active site and preferentially binds long chain fatty acids and large hydrophobic inhibitors. This discovery is significant for the treatment of P. aeruginosa infections.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Hannah M. Work, Sylvie E. Kandel, Jed N. Lampe
Summary: CYP3A7, a member of the CYP3A enzyme sub-family expressed in fetuses and neonates, plays a critical role in drug metabolism. However, it is often overlooked in preclinical drug testing. Screening for CYP3A7 inhibitors is essential to identify chemical entities with potential toxicity risks for neonates. A fluorescent compound DBF has been identified as superior for high-throughput screening, showing promise for future drug screening in the neonatal population.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Amanda Jack, Luke S. Ferro, Michael J. Trnka, Eddie Wehri, Amrut Nadgir, Xammy Nguyenla, Douglas Fox, Katelyn Costa, Sarah Stanley, Julia Schaletzky, Ahmet Yildiz
Summary: Research shows that the N protein of SARS-CoV-2 forms biomolecular condensates with viral genomic RNA, facilitating packaging of the RNA genome into viral particles. This process is influenced by interactions within the N protein, which can be disrupted by small molecules.
Article
Biology
Mariah L. Hoye, Lorenzo Calviello, Abigail J. Poff, Nna-Emeka Ejimogu, Carly R. Newman, Maya D. Montgomery, Jianhong Ou, Stephen N. Floor, Debra L. Silver
Summary: Mutations in the DDX3X gene play a crucial role in cortical development and are associated with DDX3X syndrome. The study shows that DDX3X controls translational and cell cycle control of neural progenitors, influencing neurogenesis and cortical development.
Article
Biochemistry & Molecular Biology
Michaela Hvizdak, Sylvie E. Kandel, Hannah M. Work, Emily G. Gracey, Rebecca L. McCullough, Jed N. Lampe
Summary: Per- and polyfluoroalkyl substances (PFAS) are highly stable fluorinated compounds used in consumer products, and their environmental persistence leads to human exposure and bioaccumulation. Prenatal PFAS exposure is linked to adverse birth outcomes and developmental defects. The CYP3A7 enzyme, responsible for fetal development, is hypothesized to be inhibited by PFAS compounds.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Biology
Beata Malachowska, Weng-Lang Yang, Andrea Qualman, Israel Muro, Devin M. Boe, Jed N. Lampe, Elizabeth J. Kovacs, Juan-Pablo Idrovo
Summary: In a mouse model of skin burn, the liver plays a differential role in young and aged mice, with the liver of aged animals being more susceptible. Understanding the aged-specific liver response to burns is crucial for improving healthcare.
COMMUNICATIONS BIOLOGY
(2023)
Editorial Material
Multidisciplinary Sciences
Yizhu Lin, Stephen N. Floor
Article
Biochemical Research Methods
Yizhu Lin, Samentha Kwok, Abigail E. Hein, Bao Quoc Thai, Yewande Alabi, Megan S. Ostrowski, Ke Wu, Stephen N. Floor
Summary: This study developed a platform for directed evolution of RNA molecular recorders and engineered an RNA A-to-I deaminase with high activity, low bias, and low background noise. By using this deaminase, they were able to write a molecular record of RNA-protein interactions and measure binding on single messenger RNAs. They discovered competition between PUM1 and PUM2 proteins for certain binding sites as well as transcript isoform-specific RNA-protein interactions.
Review
Biochemistry & Molecular Biology
Margaret Gadek, Elliott H. Sherr, Stephen N. Floor
Summary: RNA molecules rely on proteins, such as DDX3X and its paralog DDX3Y, for their life cycle and their dysregulation is implicated in various diseases including cancer and DDX3X syndrome. DDX3X-linked diseases often show sex differences, possibly due to differential expression or function of DDX3X and DDX3Y. Understanding the role of DDX3X in normal and disease states will help in the development of DDX3X-targeted treatments.
TRENDS IN MOLECULAR MEDICINE
(2023)
Meeting Abstract
Biophysics
Hannah M. Work, Sylvie E. Kandel, Jed N. Lampe
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Jed Lampe
Meeting Abstract
Biochemistry & Molecular Biology
Emily Hicks, Sylvie Kandel, Jed Lampe