Article
Biotechnology & Applied Microbiology
Ru-Yi Ye, Juan Song, Zhi-Jun Zhang, Hui-Lei Yu
Summary: CYP120As are unique non-membrane P450 enzymes that play a significant role in the biodegradation of retinoids, with promising catalytic potential.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Freeborn Rwere, Sangchoul Im, Lucy Waskell
Summary: By altering the 140s FMN binding loop of CYPOR, the activity with cyt P450s can be affected, with the mutant activity primarily determined by its ability to reduce ferric cyt P450. The different behaviors of the mutants are mainly due to the altered structure and mobility of the loop.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biotechnology & Applied Microbiology
Lihong Jiang, Lei Huang, Jin Cai, Zhinan Xu, Jiazhang Lian
Summary: This article discusses the strategies for improving the expression and activity of eukaryotic P450s in yeast, followed by examples of P450s involved in biosynthetic pathway engineering.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
Article
Biochemistry & Molecular Biology
Narayanan Srividya, Iris Lange, Jana K. Richter, Matthias Wuest, B. Markus Lange
Summary: In this study, the enantioselectivity of multiple enzymes involved in monoterpenoid biosynthesis in peppermint and Japanese catnip was investigated. The experimental results showed that these enzymes exhibited different enantioselectivity towards intermediates of the pathway, and molecular modeling studies supported the experimental data. This study lays the groundwork for further structure-function studies on the origin of enantioselectivity in closely related species of the Lamiaceae.
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
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
Medical Laboratory Technology
Mindy Kohlhagen, Surendra Dasari, Maria Willrich, MeLea Hetrick, Brian Netzel, Angela Dispenzieri, David L. Murray
Summary: The study describes an automated Mass-Fix method based on MALDI-TOF MS as a replacement for traditional gel-based immunofixation. After validation, Mass-Fix meets the requirements of clinical laboratories, improving sample processing efficiency and identification accuracy, while reducing paper storage and resource waste.
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Nataliia Kovalchuk, Joseph L. Jilek, Laura S. Van Winkle, Nathan J. Cherrington, Xinxin Ding
Summary: The study used a lung-Cpr-null mouse model to investigate the role of lung POR in PQ-induced pulmonary fibrosis, finding that CPR plays a critical role in this process.
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
Ecology
Xiaoman Zhang, Zhiyong Shi, Cai-qing Yang, Jing Li, Jingze Liu, Ai-bing Zhang
Summary: This study identified a co-orthologous gene, CYP4g15, in insects that originated from different bacteria species, suggesting its functional conservation and ancient origin.
FRONTIERS IN ECOLOGY AND EVOLUTION
(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
Pharmacology & Pharmacy
Melina Lopez, Pedro F. Malacarne, Anna Gajos-Draus, Xinxin Ding, Andreas Daiber, Jon O. Lundberg, Stefan Offermanns, Ralf P. Brandes, Flavia Rezende
Summary: The study suggests that metabolism by vascular CYPs does not contribute to the pharmacological function of organic nitrates, while ALDH2 plays an important role in activating organic nitrates.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Justin C. Miller, Allison J. Hollatz, Mary A. Schuler
Summary: The study identifies differences in the terpene indole alkaloid (TIA) pathways in Catharanthus roseus and Camptotheca acuminata, and demonstrates the ability of specific P450 proteins to convert certain compounds in these pathways. The research provides valuable tools for further examination of substrate recognition and the unique mechanism of C-C bond scission involved in these pathways.
Article
Chemistry, Analytical
Lan Zhao, Jiaoli Tao, Yongdong Huang, Kai Zhu, Yuxiang Du, Dongxia Hao, Hongying Liu, Rongyue Zhang, Guanghui Ma
Summary: A novel nanodisc-based immobilization method was developed for high-efficient purification and reconstitution of cytochrome P450 in one step. By adjusting molar ratios of phospholipids to membrane scaffold protein, properties of charged-nanodiscs were controlled well. The method showed promising potential for one-step purification and reconstitution of membrane protein with significantly increased purity of cytochrome P450.
JOURNAL OF SEPARATION SCIENCE
(2021)
Article
Multidisciplinary Sciences
Kristine Korzow Richter, Maria C. Codlin, Melina Seabrook, Christina Warinner
Summary: Collagen peptide mass fingerprinting by MALDI-TOF-MS, also known as ZooMS, is a rapidly growing analytical technique in the fields of archaeology, ecology, and cultural heritage. It enables rapid taxonomic identification of large bone assemblages and cultural heritage objects. However, there are limitations that need to be addressed for future advancements.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Medicinal
Naoya Kitamura, Michael Dominic Sacco, Chunlong Ma, Yanmei Hu, Julia Alma Townsend, Xiangzhi Meng, Fushun Zhang, Xiujun Zhang, Mandy Ba, Tommy Szeto, Adis Kukuljac, Michael Thomas Marty, David Schultz, Sara Cherry, Yan Xiang, Yu Chen, Jun Wang
Summary: This study discovered 23R, one of the most potent and selective noncovalent SARS-CoV-2 MPpro inhibitors reported to date, and a novel binding pocket in MPpro that can be explored for inhibitor design.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Henry M. Sanders, Blagojce Jovcevski, Michael T. Marty, Tara L. Pukala
Summary: The study demonstrates that lipid membrane composition influences the aggregation of misfolding proteins and the efficacy of amyloid inhibitors. Different mechanisms were observed for two well-known polyphenol inhibitors in the presence of lipid membranes, highlighting the importance of considering lipid environments in amyloid inhibitor design.
Article
Biochemical Research Methods
Deseree J. Reid, James G. Rohrbough, Marius M. Kostelic, Michael T. Marty
Summary: Antimicrobial peptides (AMPs) are an important component of the innate immune system and have promising applications in fighting against antibiotic-resistant infections. However, studying the interactions between these peptides and lipid bilayers is challenging, which hinders the understanding of their mechanisms of toxicity and selectivity. In this study, fast photochemical oxidation of peptides and native charge detection-mass spectrometry were used to investigate the interactions between AMPs and different lipid bilayer nanodiscs. The results showed variations in peptide oxidation in different lipid environments, indicating their affinity for lipid bilayers. These findings provide valuable information on the potential modes of action and lipid selectivity of AMPs.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Biochemical Research Methods
Andrew K. Swansiger, Michael T. Marty, James S. Prell
Summary: State-of-the-art native mass spectrometry methods have provided insight into the structure and properties of noncovalent assemblies, especially for highly heterogeneous intact complexes. A new macromolecular mass defect analysis method utilizing Fourier transform has been developed, showing high accuracy in deconvoluting low-resolution data with few input parameters. This method is expected to be valuable in characterizing a wide range of analytes and reconstructing isotope profiles in complex mass spectra.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Biochemical Research Methods
Marius M. Kostelic, Chih-Chieh Hsieh, Henry M. Sanders, Ciara K. Zak, Jack P. Ryan, Erin S. Baker, Craig A. Aspinwall, Michael T. Marty
Summary: Native mass spectrometry and charge detection-mass spectrometry are versatile tools for characterizing proteins and macromolecular complexes. Researchers have improved sensitivity by modifying the surface of nanoelectrospray ionization needles with inert surface modifiers.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Biochemical Research Methods
Michael T. Marty
Summary: Mass spectrometry is a powerful tool for measuring the mass of intact proteins and other biomolecules. However, key metrics in the field are often not precisely defined. This article explores different definitions of mass, error, and uncertainty and provides recommendations for best practices.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Editorial Material
Biochemical Research Methods
Michael T. Marty
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2022)
Article
Chemistry, Analytical
Deseree J. Reid, Tapasyatanu Dash, Zhihan Wang, Craig A. Aspinwall, Michael T. Marty
Summary: Daptomycin is a cyclic lipopeptide antibiotic that interacts with lipid membranes in a non-specific manner. The interaction strength depends on membrane rigidity, with more rigid membranes showing stronger interactions. More fluid membranes may undergo pore formation to expose daptomycin to oxidation. These findings highlight the complementary use of native mass spectrometry, fast photochemical oxidation of peptides, and membrane conductance experiments in studying antibiotic-membrane interactions.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Henry M. Sanders, Farzaneh Chalyavi, Caitlyn R. Fields, Marius M. Kostelic, Ming-Hao Li, Daniel P. Raleigh, Martin T. Zanni, Michael T. Marty
Summary: The aggregation of islet amyloid polypeptide (IAPP) is associated with beta-cell dysfunction in type 2 diabetes (T2D) in humans. The interaction of IAPP oligomers with lipid membranes can disrupt the bilayer integrity and/or homeostasis of the cell. Amino acid sequence variations of IAPPs between species can greatly decrease their propensity for aggregation.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Chemistry, Analytical
Wilson Phung, Corey E. E. Bakalarski, Trent B. B. Hinkle, Wendy Sandoval, Michael T. T. Marty
Summary: Recent advances in native and denatured intact protein mass spectrometry have made them essential for biotherapeutic characterization. This paper introduces the UniDec processing pipeline (UPP) for the analysis of batched biotherapeutic intact mass spectrometry data, providing fast processing, deconvolution, and peak detection. The UPP offers a flexible workflow that can be easily customized and applied to a wide range of biotherapeutic applications.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Melanie T. Odenkirk, Guozhi Zhang, Michael T. Marty
Summary: Lipids play important roles in membrane protein structure, interactions, and activity. Nanodiscs are a suitable model for studying protein-lipid interactions in a lipid bilayer. This study investigated how nanodisc assembly conditions affect the lipid profile. The results suggest that while most lipids are unaffected, some changes occurred in specific lipid classes under certain assembly conditions.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Biochemical Research Methods
Julia A. Townsend, Michael T. Marty
Summary: Membrane proteins often form functional complexes in lipid bilayers, making it difficult to characterize their oligomerization. However, using native mass spectrometry combined with lipid nanodiscs, it is possible to study the oligomeric state distribution and lipid preferences of these complexes. This study presents a novel data analysis method using macromolecular mass defect analysis to interpret complex spectra. It also discusses the limitations and strategies to resolve ambiguities, along with recent research on antimicrobial peptides, amyloid proteins, and viroporins in lipid membranes.
Article
Chemistry, Multidisciplinary
Yun Zhu, Melanie T. Odenkirk, Pei Qiao, Tianqi Zhang, Samantha Schrecke, Ming Zhou, Michael T. Marty, Erin S. Baker, Arthur Laganowsky
Summary: By combining native mass spectrometry (MS) and lipidomics, we have developed an innovative approach to identify the lipids retained by membrane proteins from natural lipid extracts. Our findings indicate that the bacterial ammonia channel (AmtB) selectively retains specific cardiolipin (CDL) and phosphatidylethanolamine (PE) from these extracts. This research provides a new avenue to explore the important lipid-protein interactions in membrane protein structure and function.
Article
Biochemical Research Methods
Jack P. Ryan, Marius M. Kostelic, Chih-Chieh Hsieh, Joshua Powers, Craig Aspinwall, James N. Dodds, John E. Schiel, Michael T. Marty, Erin S. Baker
Summary: This article introduces a method that combines different analytical workflows to evaluate the composition and ratio of AAV capsids. The method includes two steps, each for evaluating the intact capsids and viral protein subunits. By applying this method, a better understanding of the characteristics and functions of AAV capsids can be achieved.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Chemistry, Analytical
Weijing Liu, Hiruni S. Jayasekera, James D. Sanders, Guozhi Zhang, Rosa Viner, Michael T. Marty
Summary: In this study, an online buffer exchange coupled to native mass spectrometry (OBE-nMS) technique was developed for analyzing membrane proteins in different membrane mimetics. The results showed that mobile phases containing ammonium acetate and lauryl-dimethylamine oxide were most universal for characterizing both bacterial and mammalian membrane proteins in detergent micelles. For membrane proteins in nanodiscs, ammonium acetate was sufficient as the mobile phase. This technique enables rapid measurement of each membrane protein and facilitates the assessment of their integrity prior to structural elucidation.
ANALYTICAL CHEMISTRY
(2023)