Editorial Material
Biochemistry & Molecular Biology
F. Peter Guengerich
Summary: The paper introduces the concept of cytochrome b(5) as an auxiliary protein facilitating cytochrome P450 reactions, providing important insights for future research.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Article
Biology
Jiemin Shen, Gang Wu, Ah-Lim Tsai, Ming Zhou
Summary: This study demonstrates the formation of stable binary and ternary complexes between mammalian cytochrome b(5), cytochrome b(5) reductase, and stearoyl-CoA desaturase-1, which enhance electron transfer rates.
COMMUNICATIONS BIOLOGY
(2022)
Review
Plant Sciences
Chang-Jun Liu
Summary: Cytochrome b(5) (CB5) is a small heme-binding protein that functions as an electron donor in oxidative reactions. In plants, the CB5 protein family has expanded isoform numbers and cellular functions compared to yeast and mammalian counterparts. Plant CB5 proteins are involved in fatty acid metabolism, specialized metabolite formation, and interact with non-catalytic proteins to regulate metabolic and cellular processes. The cellular and metabolic roles of plant CB5 proteins have received less attention compared to mammalian CB5 proteins. Understanding the biological functions of CB5 proteins in plants could have important implications for biotechnological applications.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Melanie Nolden, Mark J. Paine, Ralf Nauen
Summary: Cytochrome P450 monooxygenases play a crucial role in the oxidative metabolism of xenobiotics in insects and their duplication and upregulation can lead to insecticide resistance. The interaction between P450s and other enzymes like NADPH cytochrome P450 oxidoreductase and cytochrome b5 is complex and can impact metabolic capacity. Recombinant expression of P450s in insect cells with cytochrome b5 can significantly enhance their ability to metabolize certain substrates, but not necessarily insecticides like deltamethrin.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Bikash R. Sahoo, Ayyalusamy Ramamoorthy
Summary: The catalytic activity of cytochrome P450 2B4 is regulated by its redox partner cytochrome b5. The interaction between CYP2B4 and Cyt-b5 in the endoplasmic reticulum membrane plays a crucial role in substrate catalysis and reaction rate regulation. Understanding the molecular basis of their complexation in a membrane environment is important for studying the enzymatic activity of CYP2B4.
BIOPHYSICAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Lucy Darakjian, Malavika Deodhar, Jacques Turgeon, Veronique Michaud
Summary: Diabetes mellitus is a metabolic disease that can lead to serious complications, with type 2 diabetes mellitus (T2DM) being the most common form that often requires multiple medications for control. T2DM is associated with an increase in inflammatory markers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Tabish Iqbal, Debasis Das
Summary: The purification and biochemical characterization of plant cytochrome b5 and cytochrome b5 reductase provide important insights into their function and mechanism.
Review
Pharmacology & Pharmacy
Camille Lenoir, Victoria Rollason, Jules A. Desmeules, Caroline F. Samer
Summary: Inflammation has a specific impact on CYP activities, depending on the nature and severity of the underlying inflammatory disease. The drug-disease interactions can significantly affect drug pharmacokinetic parameters and clinical management. Resolution of inflammation may lead to normalization of CYP activity, but further research is needed to clarify some equivocal results.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Donghak Kim, Vitchan Kim, Yasuhiro Tateishi, F. Peter Guengerich
Summary: High-affinity binding of cytochrome b(5) (b(5)) (K-d < 100 nM) was observed with many drug-metabolizing cytochrome P450 (P450) enzymes. Evidence is provided for a ternary P450 3A4-b(5)-NADPH-P450 reductase complex, indicating the importance of ternary complexes in P450 reactions.
DRUG METABOLISM AND DISPOSITION
(2021)
Article
Multidisciplinary Sciences
Guang Mao Shen, Shi Yuan Ou, Chu He, Jie Liu, Lin He
Summary: Sequencing the full-length transcriptome of the striped flea beetle using PacBio Iso-Seq technology revealed a wealth of transcript information, including the structure of its genome and classification of detoxification enzyme coding regions.
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
Pharmacology & Pharmacy
Xu Wang, Jingjing Fa, Yuanjin Zhang, Shengbo Huang, Jie Liu, Junqing Gao, Lina Xing, Zongjun Liu, Xin Wang
Summary: There is a potential interaction between Danshen tablet and rivaroxaban as the former inhibits the metabolism of the latter. This may be due to the strong inhibitory effects of Danshen tablet's components, particularly dihydrotanshinone I, on CYP enzymes. Therefore, drug monitoring and dosage adjustment are necessary when Danshen tablet and rivaroxaban are used simultaneously in clinical practice.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Robert Hall, Shuai Yuan, Katherine Wood, Mate Katona, Adam C. Straub
Summary: The CYB5R family of flavoproteins plays a crucial role in regulating redox balance in cells, with CYB5R3 being associated with various diseases. While CYB5R3 has been extensively studied, the other members of the CYB5R family remain understudied, presenting an opportunity to uncover their critical functions in physiology and disease.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Naoki Katayama, Keiichi Odagiri, Akio Hakamata, Chiaki Kamiya, Shinya Uchida, Shimako Tanaka, Naoki Inui, Noriyuki Namiki, Koichiro Tatsumi, Hiroshi Watanabe
Summary: This study investigated the impact of clopidogrel on the pharmacokinetics of selexipag and its active metabolite in 14 healthy Japanese volunteers. The results showed that co-administration of clopidogrel with selexipag did not affect selexipag's pharmacokinetics, but significantly increased the AUC(0-infinity) of ACT-333679. Furthermore, even when selexipag was administered 1 day after discontinuation of clopidogrel, there was still an increase in the AUC(0-infinity) of ACT-333679, indicating a persistent inhibitory effect of clopidogrel on CYP2C8.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Mohd Faheem Khan, Cormac D. Murphy
Summary: Cunninghamella spp. fungi were used to model the metabolism of fluorinated pyrethroid pesticides, generating mammalian-equivalent metabolites of transfluthrin and beta-cyfluthrin. The fungi were found to be able to replicate the biotransformation process of fluorinated pesticides in a manner similar to mammalian metabolism.
Review
Chemistry, Multidisciplinary
Danilo Milardi, Ehud Gazit, Sheena E. Radford, Yong Xu, Rodrigo U. Gallardo, Amedeo Caflisch, Gunilla T. Westermark, Per Westermark, Carmelo La Rosa, Ayyalusamy Ramamoorthy
Summary: The possible link between hIAPP accumulation and beta-cell death in diabetic patients has sparked a lot of research on amyloid structures and aggregation pathways. Recent studies have highlighted the importance of early oligomeric intermediates and their interactions with lipid membranes, pH, insulin, and zinc in the mechanism of hIAPP aggregation. Challenges in characterizing the aggregation process have led to the development of various biophysical and chemical approaches, with studies suggesting that restoring hIAPP proteostasis could be a promising strategy for therapy.
Review
Chemistry, Multidisciplinary
Phuong H. Nguyen, Ayyalusamy Ramamoorthy, Bikash R. Sahoo, Jie Zheng, Peter Faller, John E. Straub, Laura Dominguez, Joan-Emma Shea, Nikolay Dokholyan, Alfonso De Simone, Buyong Ma, Ruth Nussinov, Saeed Najafi, Son Tung Ngo, Antoine Loquet, Mara Chiricotto, Pritam Ganguly, James McCarty, Mai Suan Li, Carol Hall, Yiming Wang, Yifat Miller, Simone Melchionna, Birgit Habenstein, Stepan Timr, Jiaxing Chen, Brianna Hnath, Birgit Strodel, Rakez Kayed, Sylvain Lesne, Guanghong Wei, Fabio Sterpone, Andrew J. Doig, Philippe Derreumaux
Summary: Protein misfolding and aggregation are common in amyloidogenic diseases, and understanding how amyloid species become toxic is crucial for treatment development. Experiments using computer modeling, in vitro and in vivo studies, as well as pharmacology, have provided valuable insights into the accumulation and deposition of amyloid species, contributing to research on diseases like Alzheimer's, Parkinson's, diabetes, and ALS.
Article
Chemistry, Multidisciplinary
Srikar Munukutla, Alec Bertoy, Stephen Rush, Ayyalusamy Ramamoorthy
Summary: This study presents a method to convert NMR spectra into piano notes and create a library of molecule-inspired tunes. This supplementary approach can contribute to a more inclusive learning atmosphere for all students in the classroom.
JOURNAL OF CHEMICAL EDUCATION
(2022)
Article
Chemistry, Physical
Samuel D. McCalpin, Thirupathi Ravula, Ayyalusamy Ramamoorthy
Summary: This study demonstrates the formation of lipid nanodiscs using nonionic glycoside natural products called saponins and phospholipid DMPC. The effect of different saponin/lipid ratios on the properties of nanodiscs was investigated. The results show that a high saponin/lipid ratio reduces the size of nanodiscs and decreases their ability to align in a magnetic field.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Thirupathi Ravula, Ayyalusamy Ramamoorthy
Summary: Recent advances in lipid nanodisc technology have addressed challenges in studying membrane proteins and drug delivery. Using synthetic amphiphilic polymers, researchers successfully aligned large-size polymer nanodiscs for high-resolution solid-state NMR studies. The use of polymer-based macro-nanodiscs as alignment media has further enabled structural studies on proteins by solution NMR spectroscopy.
Review
Biochemistry & Molecular Biology
Bankala Krishnarjuna, Ayyalusamy Ramamoorthy
Summary: Atomic-resolution structural studies of membrane-associated proteins and peptides in a membrane environment are important for understanding their biological function and disease pathology. Recent advancements in NMR spectroscopy, cryoEM approaches, and the development of novel membrane mimetics have overcome the complexity of the cell membrane and enabled reconstitution and investigation of membrane proteins.
Article
Chemistry, Analytical
Bankala Krishnarjuna, Sang -Ghoul Im, Thirupathi Ravula, Joseph Marte, Richard J. Auchus, Ayyalusamy Ramamoorthy
Summary: This study reports the successful functional reconstitution of a membrane-bound redox complex in non-ionic inulin-based polymer nanodiscs. The nanodiscs have a higher phase-transition temperature and can align in an externally applied magnetic field. These findings suggest that non-ionic polymer nanodiscs can be used for studying the function and structures of various membrane proteins/complexes.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yoel A. Klug, Roland Schwarzer, Thirupathi Ravula, Etai Rotem, Ayyalusamy Ramamoorthy, Yechiel Shai
Summary: In this study, calcium interaction motifs (CIMs) in the gp41 CHR and NHR regions were discovered via NMR spectroscopy. The assembly of CHR-NHR SHB was found to be facilitated in Ca2+-containing media and impaired in CIM mutants. The clinically approved fusion inhibitor T20 exhibited reduced inhibitory efficiency when challenged with calcium, which could have implications for the development of better fusion inhibitors for HIV.
Review
Chemistry, Multidisciplinary
Yusuke Nishiyama, Guangjin Hou, Vipin Agarwal, Yongchao Su, Ayyalusamy Ramamoorthy
Summary: Solid-state NMR spectroscopy is a commonly used technique for studying the atomic-resolution structure and dynamics of various systems. However, its spectral resolution and sensitivity have been limited. The development of ultrafast-MAS technology has provided opportunities to improve the resolution and sensitivity of solid samples. Despite the limitations and challenges, ultrafast-MAS NMR techniques have achieved remarkable results in various fields.
Article
Biochemistry & Molecular Biology
Bankala Krishnarjuna, Thirupathi Ravula, Edgar M. Faison, Marco Tonelli, Qi Zhang, Ayyalusamy Ramamoorthy
Summary: In this study, polymer-based nanodiscs were used to measure RDCs from nucleic acids. The nanodiscs were characterized and their alignment stability was confirmed. RDCs from a labeled nucleic acid molecule were successfully measured using the aligned nanodiscs. This demonstrates the potential of SMA-EA-based lipid-nanodiscs for structural and dynamical studies of nucleic acids.
Article
Chemistry, Multidisciplinary
Pei Yang, Wen Guo, Ayyalusamy Ramamoorthy, Zhan Chen
Summary: There is significant interest in developing antimicrobial compounds to overcome bacterial resistance to conventional antibiotics. MSI-594 is a synthetic peptide with broad spectrum antimicrobial activity. Investigating how MSI-594 disrupts the cell membrane is important for understanding its mechanism of action.
Article
Chemistry, Physical
Samuel D. McCalpin, Malitha C. Dickwella Widanage, Riqiang Fu, Ayyalusamy Ramamoorthy
Summary: We developed a new method using magic angle spinning (MAS) to produce stable intermediates of the islet amyloid polypeptide associated with type-2 diabetes. These intermediates were a heterogeneous mixture of globular and rod-like species with beta-sheet structure and the ability to seed fibrillation. Our findings suggest that this methodology can be applied to studying other aggregating systems.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Materials Science, Multidisciplinary
Jiwon Lim, Shuo Zhang, Luyang Wang, Deokwon Seo, Malitha C. Dickwella Widanage, Kevin P. Pipe, Ayyalusamy Ramamoorthy, Jinsang Kim
Summary: DHI-free PCA coating using 3,4-dihydroxybenzylamine hydrobromide provides a smooth and uniform surface with preserved primary amine groups, offering an alternative strategy for surface amine functionalization. Additionally, DHI-free PCA improves the thermal conductivity of graphene-polymer composites.
ACS APPLIED POLYMER MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Bankala Krishnarjuna, Thirupathi Ravula, Ayyalusamy Ramamoorthy
Summary: In this study, the membrane-anchored flavin mononucleotide binding domain (FBD) of CYP450 reductase was extracted in E. coli lipid-nanodiscs using charge-free pentyl-inulin polymer. The FBD in nanodiscs showed conformational homogeneity and enabled high-resolution NMR probing. P-31 NMR revealed that the polymer had no preference for any specific E. coli lipids and identified the lipid types in the nanodiscs.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Thirupathi Ravula, Ayyalusamy Ramamoorthy
Summary: A family of non-ionic amphiphilic polymers synthesized by hydrophobic functionalization of fructo-oligosaccharides/inulin is reported, which enhances the interaction efficiency between lipid nanodiscs and proteins, and exhibits stability, alignment properties, and unprecedented efficiency in extracting membrane proteins.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
