Review
Chemistry, Physical
Donya Valikhani, Juan M. Bolivar, Joelle N. Pelletier
Summary: Cytochrome P450s are a large superfamily of heme proteins with important applications in drug metabolism studies and biocatalytic transformations. Immobilization of P450 enzymes on biosensing platforms and in biocatalytic reactions plays a key role in improving operational stability. Various methods and materials have been developed to address the challenges associated with the unique characteristics of P450s in different applications.
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
Multidisciplinary Sciences
Dusan Zivkovic, Angelique Sanchez Dafun, Thomas Menneteau, Adrien Schahl, Sandrine Lise, Christine Kervarrec, Ana Toste Rego, Paula C. A. da Fonseca, Matthieu Chavent, Charles Pineau, Odile Burlet-Schiltz, Julien Marcoux, Marie-Pierre Bousquet
Summary: During spermatogenesis, the proteasome plays a crucial role in regulating cell division processes. The s20S proteasome becomes highly active during meiosis, mainly through 19S activation and PA200 binding. The proteasome population shifts from c20S to s20S during differentiation, and s20S interacts with components of the meiotic synaptonemal complex. In vitro, s20S shows higher trypsin- and chymotrypsin-like activities and displays structural differences between alpha 4 and alpha 4s.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
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
Pharmacology & Pharmacy
Guodong Chen, Li Tao, Zhengjian Li
Summary: Molecular characterization of higher order structure in protein therapeutics is essential for various aspects in drug discovery and development. Recent advances in mass spectrometry offer orthogonal ways to characterize this structure and can be utilized for epitope mapping, aggregation assessment, and comparability studies. Future trends in applying these MS methods to HOS characterization are also discussed.
DRUG DISCOVERY TODAY
(2022)
Article
Biochemistry & Molecular Biology
Dana Felker, Haoming Zhang, Zhiyuan Bo, Miranda Lau, Yoshihiro Morishima, Santiago Schnell, Yoichi Osawa
Summary: Covalent crosslinking and mass spectrometry techniques show promise in studying multiprotein complexes, with a study using CYP102A1 homodimer to identify inter-monomer crosslinks through limited crosslinking and monomer isolation. By examining 31 unique crosslinks, validation of cryo-EM structures and new conformations of CYP102A1 were achieved.
BIOPHYSICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Thomas Tran, Aruni P. K. K. Karunanayake Mudiyanselage, Stephen J. Eyles, Lynmarie K. Thompson
Summary: Motile bacteria can sense their environment and swim towards favorable conditions using a chemotaxis system. In this system, ligand binding to the chemoreceptor triggers a phosphorylation cascade that controls flagellar rotation. By studying functional signaling complexes in E. coli, it was found that stabilization/destabilization of certain domains in CheA is crucial for modulating its kinase activity in chemotaxis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Arsenij Kokorin, Vlada B. Urlacher
Summary: In this study, fusion of P450 BM3 from Bacillus megaterium and an alcohol dehydrogenase from Sphingomonas yanoikuyae improved the two-step oxidation of (+)-valencene and resulted in increased production of (+)-nootkatone.
Article
Biotechnology & Applied Microbiology
Li Ma, Tianjian Sun, Yunjie Liu, Yue Zhao, Xiaohui Liu, Yuxuan Li, Xinwei Chen, Lin Cao, Qianqian Kang, Jiawei Guo, Lei Du, Wei Wang, Shengying Li
Summary: In this study, cytochrome P450 BM3 was engineered into peroxygenases through directed evolution. These modified enzymes were used to selectively oxidize indole derivatives to produce a variety of indigoid pigments with a reduced band gap. These indigoid photocatalysts show promise for the development of new organic electronic devices.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2023)
Article
Food Science & Technology
Mulin Fang, Zhe Wang, Kathleen Norris, Judith A. James, Si Wu, Kenneth Smith
Summary: This study demonstrates the utility of a new analysis platform for mapping antibody-antigen epitopes and discovers a novel binding mechanism for highly neutralizing fully human antibodies to anthrax protective antigen. These findings are crucial for the development of novel therapeutics against anthrax.
Article
Chemistry, Analytical
Bassam Lajin, Natascha Schweighofer, Walter Goessler, Barbara Obermayer-Pietsch
Summary: The developed UHPLC-ESIMS/MS method enables the rapid and sensitive determination of caffeine and paraxanthine in biological samples. It offers a 10-fold improvement in detection limit, rapid chromatographic separation, the use of a green chromatographic solvent, direct determination with little sample preparation, and accuracy ensured by isotopically labeled internal standards and qualifier ions. This method is suitable for large clinical studies and provides multiple advantages over current methods.
Article
Biochemistry & Molecular Biology
Sarah M. Glass, Stephany N. Webb, F. Peter Guengerich
Summary: Among the 57 human cytochrome P450 enzymes, seven are mitochondrial and utilize an electron transport system with adrenodoxin (Adx) and NADPHadrenodoxin reductase (AdR) to mediate protein interactions through electrostatic interactions. Experimental and computational studies have shown that despite some differences in interactions, the binding between P450 and Adx is P450-specific.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Chemistry, Analytical
Shuai Yan, Dongqing Zhao, Chunqing Wang, Hao Wang, Xinyu Guan, Yan Gao, Xiangyang Zhang, Ning Zhang, Ruibing Chen
Summary: This study established an analytical strategy to characterize RNA-binding proteins from different subcellular regions, identifying a large number of known and novel RBPs and cataloging their subcellular localizations. The observation of metabolic enzymes as RBPs highlights the potential role of RNA-binding in regulating cellular metabolism.
ANALYTICA CHIMICA ACTA
(2021)
Article
Biochemistry & Molecular Biology
Yoo-Bin Lee, Vitchan Kim, Sung-Gyu Lee, Gyu-Hyeong Lee, Changmin Kim, Eunseo Jeong, Donghak Kim
Summary: This study demonstrates that allelic variations of human cytochrome P450 2C8 can significantly affect drug metabolism and the production of fatty acid-derived signal molecules. Functional analysis of four newly identified allelic variants showed that V181I, I244V, and L361F variants resulted in a significant reduction in enzyme activity. The L361F variant also exhibited a significant decrease in the efficiency of arachidonic acid epoxidation reactions. These findings suggest that individuals carrying these newly identified P450 2C8 allelic variations may have altered metabolism of clinical medicines and fatty acid-derived signal molecules.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Plant Sciences
Silke von Horsten, Lars-Oliver Essen
Summary: Phytochrome activity is regulated not only by light but also by post-translational modifications such as phosphorylation. PAPP5 is a phosphatase responsible for the dephosphorylation of plant phytochromes, and its activation by arachidonic acid leads to conformational changes in the TPR region. Molecular dynamics analysis shows that a C-terminal motif in PAPP5 is associated with restricting the orientation of the TPR region relative to the catalytic PP2A domain when complexed with a phyB phosphopeptide. These findings suggest a high degree of conservation in the activation mode of PPP-type protein phosphatases between plants and mammals.
FRONTIERS IN PLANT SCIENCE
(2021)
Review
Chemistry, Multidisciplinary
Niklas Geue, Richard E. P. Winpenny, Perdita E. Barran
Summary: This review introduces the commonly used structural characterisation techniques in supramolecular chemistry, focusing on the strengths and weaknesses of these methods, and illustrating the benefits of using complementary techniques simultaneously through case studies.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Chemistry, Multidisciplinary
Antonio Angelastro, Alexey Barkhanskiy, Ashley P. Mattey, Edward G. Pallister, Reynard Spiess, William Goundry, Perdita Barran, Sabine L. Flitsch
Summary: A glycoengineering methodology was developed to generate antibody drug conjugates with high drug loading by combining enzymatic galactosylation and oxidation with biorthogonal tandem Knoevenagel-Michael addition chemistry.
Article
Infectious Diseases
Laura N. Jeffreys, Shaun H. Pennington, Jack Duggan, Claire H. Caygill, Rose C. Lopeman, Alastair F. Breen, Jessica B. Jinks, Alison Ardrey, Samantha Donnellan, Edward Patterson, Grant L. Hughes, David W. Hong, Paul M. O'Neill, Ghaith Aljayyoussi, Andrew Owen, Stephen A. Ward, Giancarlo A. Biagini
Summary: This study assessed the in vitro synergistic interaction between remdesivir and ivermectin, demonstrating enhanced antiviral activity against severe acute respiratory syndrome coronavirus-2. Further investigation is warranted despite the current inability to clinically apply this combination treatment strategy.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2022)
Article
Chemistry, Multidisciplinary
Emma L. Norgate, Rosie Upton, Kjetil Hansen, Bruno Bellina, C. Brookes, Argyris Politis, Perdita E. Barran
Summary: This study investigates the conformational changes of antibodies at different temperatures using variable-temperature ion mobility mass spectrometry. It is found that at lower temperatures, the structure of the antibodies does not rearrange, while within a certain temperature range, the changes in the strength of intermolecular interactions lead to restructuring.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biology
Lenin Gonzalez-Paz, Maria Jose Alvarado, Maria Laura Hurtado-Leon, Carla Lossada, Joan Vera-Villalobos, Marcos Lorono, J. L. Paz, Laura N. Jeffreys, F. Javier Torres, Ysaias J. Alvarado
Summary: This study investigates the susceptibility of respiratory tract cells to SARS-CoV-2 infection by examining the interaction between the virus and potential receptors on host cell membranes. The research predicts cell susceptibility based on the type, number, and expression level of specific receptors. Additionally, the study explores the impact of artificial environments on receptor accessibility and reveals a correlation between protein expression, diffusivity, and favorable interactions with the viral spike. The findings suggest potential sites of early infection beyond the lungs.
COMPUTERS IN BIOLOGY AND MEDICINE
(2022)
Article
Multidisciplinary Sciences
Matthew Russell, Andrew Currin, William Rowe, Guo-Qiang Chen, Perdita Barran, Nigel S. Scrutton
Summary: Despite its environmental benefits, biomanufacturing is not financially competitive compared to the carbon emitting chemical industry. The use of novel organisms, such as halophilic bacteria, can help reduce costs by thriving in environments unsuitable for other organisms. However, the lack of annotation for these organisms requires rapid characterization and data sharing to facilitate their adoption in biomanufacturing.
Article
Chemistry, Analytical
Jakub Ujma, Jacquelyn Jhingree, Emma Norgate, Rosie Upton, Xudong Wang, Florian Benoit, Bruno Bellina, Perdita Barran
Summary: The gas phase is an ideal laboratory for studying protein structure, allowing the examination of stable and transient forms of ions without solvent. By studying ubiquitin, lysozyme, and alpha-synuclein, researchers have observed temperature-dependent conformational transitions and cold denaturation in proteins.
ANALYTICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Cecile F. Frampas, Katie Longman, Matt Spick, Holly-May Lewis, Catia D. S. Costa, Alex Stewart, Deborah Dunn-Walters, Danni Greener, George Evetts, Debra J. Skene, Drupad Trivedi, Andy Pitt, Katherine Hollywood, Perdita Barran, Melanie J. Bailey
Summary: Saliva metabolomics, particularly amino acids, can differentiate between high severity and low severity COVID-19 patients, expanding the understanding of COVID-19 metabolic dysregulation and potentially providing a non-invasive means of sampling patients for timely treatment.
Article
Medical Laboratory Technology
Jenny Hallqvist, Dan Lane, Andrew Shapanis, Kayleigh Davis, Wendy E. Heywood, Ivan Doykov, Nana Ghansah, Brian Keevil, Pankaj Gupta, Rebekah Jukes-Jones, Raj Singh, Dominic Foley, Johannes P. C. Vissers, Rebecca Pattison, Samantha Ferries, Robert Wardle, Amy Bartlett, Lisa J. Calton, Leigh Anderson, Morteza Razavi, Terry Pearson, Matt Pope, Richard Yip, Leong L. Ng, Benjamin Nicholas, Alistair Bailey, Dan Noel, R. Neil Dalton, Simon Heales, Christopher Hopley, Andrew R. Pitt, Perdita Barran, Kevin Mills, Paul Skipp, Rachel S. Carling
Summary: The UK's Department of Health and Social Care established the Moonshot programme in 2020 to fund diagnostic approaches for detecting SARS-CoV-2. This study presents a targeted protein assay that utilizes mass spectrometry to accurately detect the virus in nasopharyngeal swabs. The assay shows high sensitivity and specificity compared to the commonly used RT-qPCR method.
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
(2023)
Article
Chemistry, Inorganic & Nuclear
Niklas Geue, Tom S. Bennett, Lennart A. I. Ramakers, Grigore A. Timco, Eric J. L. McInnes, Neil A. Burton, P. B. Armentrout, Richard E. P. Winpenny, Perdita E. Barran
Summary: After the electrospray ionization, analytes usually enter the gas phase with a charge-carrying ion, which is necessary for detection in the mass spectrometer. These charge carriers may not have much effect in solution, but they can significantly alter the properties of the analytes in the gas phase. By measuring their influence on the target molecule, we can gain insights into the structure and stability of the analyte. In this study, ion mobility mass spectrometry and density functional theory are used to investigate the impact of charge carriers and water on the disassembly, stability, and conformation of various metal-containing compounds.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Laura N. Jeffreys, Alison Ardrey, Taghreed A. Hafiz, Lauri-Anne Dyer, Ashley J. Warman, Nada Mosallam, Gemma L. Nixon, Nicholas E. Fisher, W. David Hong, Suet C. Leung, Ghaith Aljayyoussi, Jaclyn Bibby, Deepak V. Almeida, Paul J. Converse, Nader Fotouhi, Neil G. Berry, Eric L. Nuermberger, Anna M. Upton, Paul M. O'Neill, Stephen A. Ward, Giancarlo A. Biagini
Summary: This study successfully expressed Mycobacterium tuberculosis cytochrome bd oxidase and identified a series of inhibitors that can effectively suppress bacterial growth, suggesting their potential as antitubercular agents.
ACS INFECTIOUS DISEASES
(2023)
Review
Chemistry, Multidisciplinary
Emilia Christofi, Perdita Barran
Summary: The investigation of macromolecular biomolecules with ion mobility mass spectrometry (IM-MS) techniques has provided substantial insights into the field of structural biology. An IM-MS workflow can provide mass, charge, and conformation information of a given target analyte, which is crucial for studying protein structures. This review focuses on the analysis of proteins and their complexes using IM-MS, discussing the typical features of an IM-MS experiment and how the data can be interpreted and compared with computational tools. The review also highlights the benefits of coupling mobility analysis to activation methods and its application to the study of conformationally dynamic and intrinsically disordered proteins.
Article
Chemistry, Multidisciplinary
Daniel J. Bell, Tongtong Zhang, Niklas Geue, Ciaran J. Rogers, Perdita E. Barran, Alice M. Bowen, Louise S. Natrajan, Imogen A. Riddell
Summary: Multinuclear, self-assembled lanthanide complexes have potential as sensors and imaging agents, but synthetic and characterization challenges hinder their systematic study. This study evaluates the effect of ligand backbone symmetry on self-assembly of multinuclear lanthanide complexes, presenting an unusual Ln(6)L(6) architecture.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Review
Endocrinology & Metabolism
C. Gehin, J. Tokarska, S. J. Fowler, P. E. Barran, D. K. Trivedi
Article
Chemistry, Multidisciplinary
Manuel David Peris-Diaz, Alexey Barkhanskiy, Ellen Liggett, Perdita Barran, Artur Krezel
Summary: Ion mobility-mass spectrometry (IM-MS) revealed different conformational stability in Zn4-7-metallothionein-2. A new molecular dynamics simulation approach was introduced, which explored all conformational space, confirmed experimental data, and revealed that both Zn-S bonds and alpha-beta domain interactions modulate protein unfolding.
CHEMICAL COMMUNICATIONS
(2023)