Article
Biochemistry & Molecular Biology
Francesca Sacco, Matteo Tarchi, Giarita Ferraro, Antonello Merlino, Giorgio Facchetti, Isabella Rimoldi, Luigi Messori, Lara Massai
Summary: The study investigated the reactions of three novel platinum(II) complexes with model proteins through ESI MS analysis, revealing diverse reactivity patterns depending on the nature of the Pt complex and interacting proteins. The formation of protein-bound Pt fragments was identified, and crystal structures were used to determine the exact location of Pt binding sites, contributing to understanding the potential mechanisms of action of these innovative anticancer Pt complexes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Matthew P. Sullivan, Monika Cziferszky, Iogann Tolbatov, Dianna Truong, Davide Mercadante, Nazzareno Re, Ronald Gust, David C. Goldstone, Christian G. Hartinger
Summary: Metal complexes exhibit different binding behaviors with proteins, with Ru and Rh complexes targeting surface l-histidine residues, while Os and Ir derivatives predominantly located in electronegative binding pockets after ligand exchange. Computational studies support the binding profiles and suggest the role of protein microenvironment in eliciting selectivity for specific binding sites on the protein.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Stefano Barbera, Luisa Raucci, Giusy Tassone, Laura Tinti, Filippo Prischi, Annalisa Santucci, Maurizio Mongiat, Gian Marco Tosi, Federico Galvagni, Anna Dimberg, Cecilia Pozzi, Maurizio Orlandini
Summary: Blocking the signaling activated by the plasma membrane receptor CD93 has been shown to be useful in antiangiogenic treatment and oncotherapy. CD93 structurally exists as a dimer in endothelial cells and its oligomeric form is important for binding to its ligand Multimerin-2. Crystallographic analysis reveals the role of the C-type lectin-like and sushi-like domains in achieving a functional binding state, which provides valuable information for the development of drugs targeting CD93 in neovascular pathologies.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Analytical
Martijn M. Vanduijn, Hendrik-Jan Brouwer, Pablo Sanz de la Torre, Jean-Pierre Chervet, Theo M. Luider
Summary: The research team reported an improved electrochemical method that achieves complete reduction of both intermolecular and intramolecular disulfide bridges in a set of monoclonal antibodies. The method utilizes an online electrochemical flow cell to provide information on the pairing of heavy and light chains in the antibodies. The complete reduction of intramolecular disulfide bridges is important for the intact mass of the antibody chain and the confirmation of the protein's amino acid sequence.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Joshua N. Whitehead, Nicole G. H. Leferink, Gajendar Komati Reddy, Colin W. Levy, Sam Hay, Eriko Takano, Nigel S. Scrutton
Summary: This study presents the crystal structure of ScCubS and investigates its catalytic mechanism. The findings reveal that specific residues can control the reaction chemistry and product formation, enabling the reengineering of ScCubS. This highlights the importance of mechanistic understanding of cation stabilization in TSs for guiding catalytic outcomes.
Article
Chemistry, Multidisciplinary
Oliver J. Hale, Helen J. Cooper
Summary: This study demonstrates a mass spectrometry analysis method for the direct analysis of intact oligomeric membrane proteins from tissue. By characterizing protein assembly directly from sheep eye lens sections without sample pre-treatment, our approach allows for simultaneous analysis of soluble protein assemblies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Alejandra A. Carriles, Alberto Mills, Maria-Jose Munoz-Alonso, Dolores Gutierrez, Juan M. Dominguez, Juan A. Hermoso, Federico Gago
Summary: Mutations in the EEF1A2 gene can lead to epilepsy and severe neurological disabilities in children. The study of the crystal structure of the eEF1A2 protein provides insights into its interaction with binding partners and its anchoring points to cellular membranes. Bioinformatic and molecular modeling reveal the multifaceted role of eEF1A2 in cellular functions.
Article
Multidisciplinary Sciences
Xiaowen Liu, Zhuxin Dong, Gregory Timp
Summary: This article introduces a method of reading protein sequences using sub-nanometer pores and presents computational methods for processing nanospectra and predicting theoretical nanospectra.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Carlo Frederico Moro, Fabio C. S. Nogueira, Carlos Gabriel Moreira Almeida, Rafael Real-Guerra, Pedro Ferrari Dalberto, Cristiano V. Bizarro, Rodrigo Ligabue-Braun, Celia R. Carlini
Summary: Ureases catalyze the hydrolysis of urea into carbamate and ammonia. Most plant ureases are composed of hexamers of a single chain subunit. Canatoxin, a neurotoxic protein isolated from jack bean seeds, was found to be a lower molecular mass and less active isoform of the abundant jack bean urease (JBU). Stabilization of Canatoxin was achieved by treatment with low concentration of formaldehyde, preventing its oligomerization. Peptide analysis and de novo sequencing confirmed that Canatoxin is an isoform of JBU, and formaldehyde treatment modified amino acids at the protein's surface to prevent hexamer formation and inactive aggregation.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Analytical
Harvey E. Johnston, Kranthikumar Yadav, Joanna M. Kirkpatrick, George S. Biggs, David Oxley, Holger B. Kramer, Rahul S. Samant
Summary: Complete and reproducible extraction of protein is crucial for proteome analysis. Solvent precipitation SP3 (SP4) is proposed as an alternative method, which captures protein aggregates by centrifugation instead of magnetism. SP4 provides equivalent or higher protein yields and improved reproducibility. It also recovers more low-solubility and transmembrane proteins, offering higher recovery rates.
ANALYTICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Sarah M. Fantin, Kristine F. Parson, Pramod Yadav, Brock Juliano, Geoffrey C. Li, Charles R. Sanders, Melanie D. Ohi, Brandon T. Ruotolo
Summary: Peripheral myelin protein (PMP22) misfolding is identified as a key factor in various peripheral neuropathies. Mutant forms of PMP22 exhibit differences in stability and propensity to form homodimeric complexes compared to wild-type protein. The formation of PMP22 dimers from destabilized monomers is proposed as a key element in PMP22 mistrafficking, based on combined findings from native ion mobility-mass spectrometry and cellular data.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Xiaoran Roger Liu, Yining Huang
Summary: This article reviews several methods for studying protein structure and interactions using mass spectrometry, including hydrogen-deuterium exchange mass spectrometry, hydroxyl radical protein footprinting, and fast photochemical oxidation of proteins.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Chemistry, Multidisciplinary
Jiyeon Lee, Dahye Im, Yajie Liu, Jing Fang, Xibao Tian, Minsu Kim, Wen-Bin Zhang, Jongcheol Seo
Summary: A technique combining ion mobility spectrometry-mass spectrometry (IMS-MS) and supercharging electrospray ionization (ESI) has been demonstrated to effectively differentiate protein chemical topology. By incorporating as many charges as possible into proteins via supercharging ESI, the protein chains can be largely unfolded and stretched, revealing their hidden chemical topology. Different chemical topologies result in different geometric sizes of the unfolded proteins due to constraints in torsional rotations. The introduction of new topological indices allows for successful differentiation of various protein chemical topologies. This technique provides an easy classification of the topological features of complex proteins, previously concealed by their inherent complexity, and establishes a visual standard for discerning protein topologies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Tara K. Bartolec, Xabier Vazquez-Campos, Alexander Norman, Clement Luong, Marcus Johnson, Richard J. Payne, Marc R. Wilkins, Joel P. Mackay, Jason K. K. Low
Summary: Significant advances in cryoelectron microscopy have expanded our ability to create structural models of proteins and protein complexes. Cross-linking mass spectrometry (XL-MS) is demonstrated to be a powerful tool for high-throughput experimental assessment of protein structures and interactions. The combination of XL-MS data with AlphaFold2 predictions offers opportunities to explore the structural proteome and interactome in depth.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Samantha J. Ziegler, Sam J. B. Mallinson, Peter C. St John, Yannick J. Bomble
Summary: Microorganisms rely on protein interactions for signaling, stimuli response, and growth. Recent developments in structural biology, particularly integrative structural biology, have provided insight into how large protein complexes interact in their native environment. This mini-review discusses the past, present, and potential future of integrative structural biology in characterizing protein interactions in their cellular context.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Ethics
Hugh Davies
Summary: This paper discusses the preparations and review process conducted by the UK Research Ethics Committee (REC) for the first SARS-CoV-2 human infection challenge studies. The committee followed the guidance from the WHO and the ethical review framework of the UK Health Research Authority. The virtual meetings ensured broad representation and easy attendance for the applicants. Despite concerns of collusion, the committee made decisions independently. The review process took time, but future studies will be expedited, and the committee may be reconvened in future emergencies.
JOURNAL OF MEDICAL ETHICS
(2023)
Letter
Medicine, General & Internal
Simon E. Kolstoe, P. Affleck, J. Cons, M. C. Davis
BMJ MILITARY HEALTH
(2023)
Article
Chemistry, Multidisciplinary
Pia Mueller, Aikaterini Vriza, Adam D. Clayton, Oliver S. May, Norman Govan, Stuart Notman, Steven V. Ley, Thomas W. Chamberlain, Richard A. Bourne
Summary: Automated platforms enable fast and efficient optimization of chemical systems with single and multiple objectives. In this study, we demonstrate the application of automated optimization platforms for chemical screening of sulfide oxidations in flow. The identification of unique optima for each substrate emphasizes the importance of rapid and individual experimental optimization for successful compound screening.
REACTION CHEMISTRY & ENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Qi Lin, Hao Lan, Chunmiao Ma, Ryan T. Stendall, Kenneth Shankland, Rebecca A. Musgrave, Peter N. Horton, Carsten Baldauf, Hans-Joerg Hofmann, Craig P. Butts, Manuel M. Mueller, Alexander J. A. Cobb
Summary: We present the first structures of an unusual helix formed by a heteromeric sequence of alpha- and delta-amino acids and demonstrate its application in catalysis. The helix formation is driven by intramolecular hydrogen bonds, but we also observed an apolar interaction that stabilizes one type of helix over another. This unique stabilization enables the alpha-residues to engage in bifunctional catalysis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Samuel L. Bourne, Franz Amann, Steven V. Ley
Summary: This article provides an overview of the factors contributing to the rise of flow chemistry in the pharmaceutical industry over the past two decades. It highlights the challenges faced by the industry and how scientific progress has helped to overcome them. Current trends and examples of progress at CARBOGEN AMCIS are discussed, giving a speculative glimpse into the future of drug development and manufacturing.
Article
Chemistry, Multidisciplinary
Tarick J. El-Baba, Corinne A. Lutomski, Sean A. Burnap, Jani R. Bolla, Lindsay A. Baker, Andrew J. Baldwin, Weston B. Struwe, Carol V. Robinson
Summary: In this study, the impact of glycans on mediating ACE2 dimerization and interactions with Spike was investigated. The researchers found that glycans play a regulatory role in ACE2 dimerization and that positive cooperativity drives ACE2 to complex with multiple Spike trimers. These findings are important for developing strategies to neutralize the virus.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Correction
Biochemistry & Molecular Biology
Rei Matsuoka, Roman Fudim, Sukkyeong Jung, Chenou Zhang, Andre Bazzone, Yurie Chatzikyriakidou, Carol V. Robinson, Norimichi Nomura, So Iwata, Michael Landreh, Laura Orellana, Oliver Beckstein, David Drew
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Hsin-Yung Yen, Ali Jazayeri, Carol Robinson
Summary: GPCRs are important drug targets due to their involvement in physiological processes. Mass spectrometry techniques, such as HDX-MS and native-MS, provide opportunities to investigate GPCR pharmacology and discover new drugs. This review highlights the potential of MS techniques for in-depth investigations of GPCR biology.
PHARMACOLOGICAL REVIEWS
(2023)
Article
Multidisciplinary Sciences
Benjamin J. Hardy, Alvaro Martin Hermosilla, Dinesh K. Chinthapalli, Carol V. Robinson, J. L. Ross Anderson, Paul Curnow
Summary: In this study, a minimal diheme membrane cytochrome was computationally designed and produced in live bacteria. The synthetic construct mimics a four-helix bundle found in respiratory complexes and has no sequence homology to natural polypeptides. This artificial membrane metalloprotein has the potential to function as an electron transfer module in both synthetic protocells and living systems.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Gabriela Dias Noske, Yun Song, Rafaela Sachetto Fernandes, Rod Chalk, Haitem Elmassoudi, Lizbe Koekemoer, C. David J. Owen, Tarick V. El-Baba, Carol Robinson, Glaucius Oliva, Andre Schutzer Godoy
Summary: The main protease of SARS-CoV-2, M-pro, is responsible for cleaving the viral polyprotein and is crucial for enzyme dimerization and activity. N-terminal cleavage is not critical for dimerization, and different types of inhibitors can affect the oligomeric states. This study provides insights into the maturation process of M-pro and how it can be targeted by inhibitors.
NATURE COMMUNICATIONS
(2023)
Article
Ethics
Hugh Davies, Rosie Munday, Maeve O'Reilly, Catriona Gilmour Hamilton, Arzhang Ardahan, Simon E. Kolstoe, Katie Gillies
Summary: Research consent processes should provide sufficient information to help potential participants make decisions. However, current research proposals often lack support for decision making, even though they provide adequate detail. To address this issue, the concept of an Information and Decision Aid (IDA) is proposed to guide the dialogue between researchers and potential participants. The IDA can be easily integrated with the Informed Consent Form to address individual concerns before formal consent is obtained.
Article
Biochemical Research Methods
Kenneth R. R. Durbin, Matthew T. T. Robey, Lilien N. N. Voong, Ryan T. T. Fellers, Corinne A. A. Lutomski, Tarick J. J. El-Baba, Carol V. V. Robinson, Neil L. L. Kelleher
Summary: Native mass spectrometry has become an important technique for determining the composition of protein complexes. However, there is a lack of software tools for comprehensive analysis of native mass spectrometry data. In this study, we introduce ProSight Native as an informatics platform that can determine the complete composition of protein complexes. We demonstrated its features by successfully determining the composition of a homotetrameric membrane complex and a heterodimer complex with associated ligands.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Hongmiao Hu, Anne-Marie M. van Roon, George E. Ghanim, Bilal Ahsan, Abraham O. Oluwole, Sew-Yeu Peak-Chew, Carol V. Robinson, Thi Hoang Duong Nguyen
Summary: Shelterin and nucleosomes interact at mammalian telomeres, but the mechanism is not yet understood. Cryo-electron microscopy was used to study the structure of a human telomeric nucleosome bound to the shelterin factor TRF1. The study revealed that TRF1 binds to unwrapped nucleosomal DNA ends by engaging both the DNA and the histone octamer, resulting in a shift in the nucleosomal DNA. Phosphorylation of TRF1 and a noncanonical DNA binding surface on TRF1 were found to be crucial for its association with telomeric nucleosomes. These findings provide important insights into shelterin-chromatin interactions and its roles at telomeres.
Article
Multidisciplinary Sciences
Luke Smithers, Oksana Degtjarik, Dietmar Weichert, Chia-Ying Huang, Coilin Boland, Katherine Bowen, Abraham Oluwole, Corinne Lutomski, Carol V. Robinson, Eoin M. Scanlan, Meitian Wang, Vincent Olieric, Moran Shalev-Benami, Martin Caffrey
Summary: This study investigates the structural changes of the enzyme apolipoprotein N-acyltransferase (Lnt) during its reaction. The study confirms the ping-pong mechanism of Lnt and explains the molecular basis for its ability to bind different substrates.
Article
Chemistry, Multidisciplinary
Ricardo Labes, Julio C. Pastre, Richard J. Ingham, Claudio Battilocchio, Henrique M. Marcon, Mariana C. F. C. B. Damiao, Duc N. Tran, Steven V. Ley
Summary: This study reports the rapid synthesis of 2-pyrazolines from aldehydes via [3 + 2] cycloaddition of unstabilised diazo species and mono and di-substituted alkenes. The development includes semi-continuous and fully continuous methods, with a fully automated compound library generation and a graphical interface for automation control.
REACTION CHEMISTRY & ENGINEERING
(2023)
