Article
Chemistry, Multidisciplinary
Manuel Cordova, Lyndon Emsley
Summary: The determination of the molecular solid structure using NMR crystallography relies on generating a comprehensive set of candidate crystal structures and comparing computed chemical shifts with experimental values. However, exploring the polymorph landscape of molecular solids requires a significant computational power, leading to a bottleneck in candidate crystal generation. This study constructs three-dimensional interaction maps using a crystal structure database with associated chemical shifts to identify structural constraints for accelerating crystal structure prediction protocols, without requiring DFT-level chemical shift computations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biology
Shu Zhou, Pontus Pettersson, Markus L. Bjorck, Hannah Dawitz, Peter Brzezinski, Lena Maler, Pia adelroth
Summary: This study presents the NMR solution structure of Cox13, revealing its dimer formation in detergent micelles mainly induced by hydrophobic interactions. The analysis of chemical shift changes upon ATP addition indicates ATP binding at a conserved region of the C terminus with considerable conformational flexibility. Overall, the results suggest that the ATP interaction may inhibit the catalytic activity of CytcO and provide insights into how ATP regulates mitochondrial respiration.
Article
Biochemistry & Molecular Biology
Belen Chaves-Arquero, Cecilia Persson, Nekane Merino, Julen Tomas-Cortazar, Adriana L. Rojas, Juan Anguita, Francisco J. Blanco
Summary: Salp15 is a protein found in the saliva of the tick Ixodes scapularis. It interferes with the cellular immune response of the mammalian host by inhibiting the activation of CD4(+) T-lymphocytes. This protein has potential therapeutic applications in immune system disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Inorganic & Nuclear
Debanjana Das, Sri Rama Koti Ainavarapu
Summary: Metalloproteins are important proteins involved in metal uptake, transport, and electron-transfer reactions. Azurin peptides, which mimic the active sites of these proteins, exhibit different spectroscopic and structural properties when binding with copper or nickel. Nickel binding induces a beta-turn and fluorescence quenching due to electron transfer, similar to the quenching observed in copper-bound peptides. These findings suggest that electron transfer plays a key role in the fluorescence quenching mechanism of metal-binding peptides.
INORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Christopher M. Furze, Ignacio Delso, Enriqueta Casal, Collette S. Guy, Chloe Seddon, Chelsea M. Brown, Hadyn L. Parker, Anjana Radhakrishnan, Raul Pacheco-Gomez, Phillip J. Stansfeld, Jesus Angulo, Alexander D. Cameron, Elizabeth Fullam
Summary: This study elucidates the mechanism of how mycobacteria transport trehalose through the LpqY-SugABC transporter using a combination of techniques, pinpointing key residues for substrate-specific recognition and identifying tolerated disaccharide modifications. These findings offer critical insights into the recycling system of the essential Mtb LpqY-SugABC transporter and provide a framework for the design of new antitubercular agents and diagnostic tools.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Anastassis Perrakis, Titia K. Sixma
Summary: AlphaFold is the most ground-breaking application of AI in science so far, promising to revolutionize structural biology, but caution is advised in its implementation.
Article
Biochemistry & Molecular Biology
Cheng Zhang, Nuria Codina, Jiazhi Tang, Haoran Yu, Nesrine Chakroun, Frank Kozielski, Paul A. Dalby
Summary: The research findings highlighted the different destabilizing pathways of protein structure under low pH and high temperature stress conditions, revealing the potential for stabilizing mutations in the CL domain and C-L-C(H)1 interface. The analysis also identified key salt bridge losses as a cause of conformational changes under different stresses, with implications for future engineering efforts to enhance stability.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Dorothy D. Majewski, Mark Okon, Florian Heinkel, Craig S. Robb, Marija Vuckovic, Lawrence P. McIntosh, Natalie C. J. Strynadka
Summary: The type III secretion system (T3SS) is a protein channel used by Gram-negative pathogenic bacteria to secrete effector proteins into host cells. Structural and biochemical data on the Salmonella enterica pilotin InvH revealed a dimerized, alpha-helical structure, which can form homodimers in solution. Studies on the interaction between pilotin InvH and its cognate secretin InvG show a predominantly hydrophobic interface.
Article
Biochemistry & Molecular Biology
Roberto Tejero, Yuanpeng Janet Huang, Theresa A. Ramelot, Gaetano T. Montelione
Summary: Recent advances in molecular modeling, particularly AlphaFold, have the potential to revolutionize structural biology, as it provides protein structure models with accuracies similar to or even better than experimental data. This holds promise for guiding the analysis of experimental data and has broader applications in the field.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Andreas Nguyen, Gerd Gemmecker, Charlotte A. Softley, Levon D. Movsisyan, Toni Pfaffeneder, Andreas Heine, Klaus Reuter, Francois Diederich, Michael Sattler, Gerhard Klebe
Summary: Understanding the structural arrangements of protein oligomers can support the design of ligands that interfere with their function in order to develop new therapeutic concepts for disease treatment. Recent studies have identified a novel twisted and functionally inactive form of the enzyme TGT and investigated the correlation between ligand-binding features and protein conformation. The findings suggest a potential new design concept for drug candidates.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yingjie Song, Siping Zhang, Zirui Ye, Yongyan Song, Lin Chen, Aiping Tong, Yongxing He, Rui Bao
Summary: This study describes a group of GNAT-Xre TA modules widely distributed among Pseudomonas species, with one member - PacT toxin positively regulating iron acquisition in Pseudomonas aeruginosa. Additionally, PacT can directly bind to Fur and attenuate its DNA-binding affinity to permit expression of downstream iron-acquisition-related genes.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Tatsuro Nishikino, Atsushi Hijikata, Seiji Kojima, Tsuyoshi Shirai, Masatsune Kainosho, Michio Homma, Yohei Miyanoiri
Summary: The FliG protein is crucial for the rotational direction switching of the flagellar motor. Through NMR and molecular dynamics simulations, this study investigated the structural changes and defect in rotational direction switching of FliG. NMR analysis revealed multiple conformations of FliG, and the G215A mutation inhibited the exchange between these conformations. Moreover, changes in intradomain orientation of FliG were induced by alterations in hydrophobic interaction networks throughout the protein. This research provides important insights into the switching mechanism of the flagellar motor.
Article
Biochemistry & Molecular Biology
Tae-Yeon Kim, Tae-Sung Yoon, Sunghyun Kang, Muhammad Afzal
Summary: mCardinal2 is a red fluorescent protein developed from the designs of mKate, mNeptune, and mCardinal. The brightness and fluorescence spectrums of mCardinal2 are influenced by its mutants, resulting in different fluorescent colors. Analysis of the crystal structures of the six variants showed that the brightness-increased variant C158D exhibited enhanced hydrogen bonds around the chromophore, while brightness-decreased variants showed diminished hydrogen bonds.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Jie Zhuang, Shihui Fan, Chenyun Guo, Liubin Feng, Huilin Wang, Donghai Lin, Xinli Liao
Summary: The article presents the crystal structure and dynamics analysis of a conserved hypothetical protein MtPC from Mycobacterium tuberculosis, laying the foundation for further research and understanding of its biological functions.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Chemistry, Analytical
Caitlin M. Quinn, Roman Zadorozhnyi, Jochem Struppe, Ivan Sergeyev, Angela M. Gronenborn, Tatyana Polenova
Summary: Fluorinated drugs are becoming increasingly popular in the pharmaceutical market. The study demonstrated the effectiveness of high-frequency F-19 MAS NMR spectroscopy for rapid analysis of fluorinated active pharmaceutical ingredients in commercial formulations of blockbuster drugs.
ANALYTICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Salima Bahri, Robert Silvers, Brian Michael, Kristaps Jaudzems, Daniela Lalli, Gilles Casano, Olivier Ouari, Anne Lesage, Guido Pintacuda, Sara Linse, Robert G. Griffin
Summary: Magic-angle spinning (MAS) NMR spectroscopy has been widely used to study the high-resolution structures of amyloid-beta (A beta) and other fibrils, but it suffers from low sensitivity. In this study, the drawbacks of MAS NMR were overcome by using two relatively recent techniques: H-1 detection and dynamic nuclear polarization (DNP). The results showed improved sensitivity and allowed for nearly complete resonance assignment and structural analysis of A beta fibrils.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemical Research Methods
Guillaume A. Petit, Biswaranjan Mohanty, Roisin M. McMahon, Stefan Nebl, David H. Hilko, Karyn L. Wilde, Martin J. Scanlon, Jennifer L. Martin, Maria A. Halili
Summary: This study identified two fragments that bind to the DsbA protein from Burkholderia pseudomallei, providing a potential starting point for the development of more potent antimicrobial compounds.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Tina Arndt, Gabriele Greco, Benjamin Schmuck, Jessica Bunz, Olga Shilkova, Juanita Francis, Nicola M. Pugno, Kristaps Jaudzems, Andreas Barth, Jan Johansson, Anna Rising
Summary: The development of miniature spider silk proteins has made large-scale fiber production economically feasible by producing stronger artificial silks. This research shows that the method can be used for economically feasible bulk-scale production.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Review
Chemistry, Multidisciplinary
Tanguy Le Marchand, Tobias Schubeis, Marta Bonaccorsi, Piotr Paluch, Daniela Lalli, Andrew J. Pell, Loren B. Andreas, Kristaps Jaudzems, Jan Stanek, Guido Pintacuda
Summary: The development of H-1 detection and fast MAS technology has led to significant breakthroughs in solid-state NMR, improving signal intensity and resolution. The switch from traditional detection methods to H-1 enables faster analysis of high molecular weight biological components and provides successful strategies for studying protein structure and conformational dynamics.
Editorial Material
Biochemistry & Molecular Biology
Medoune Sarr, Kristine Kitoka, Kellie-Ann Walsh-White, Margit Kaldmaee, Rimants Metlans, Kaspar Tars, Alessandro Mantese, Dipen Shan, Michael Landreh, Anna Rising, Jan Johansson, Kristaps Jaudzems, Nina Kronqvist
Summary: The N-terminal domain of spider silk proteins plays a crucial role in the storage and assembly of spider silk. In this study, the solution and crystal structures of the N-terminal domain of the flagelliform spidroin were determined. It was found that the electrostatic intermolecular interaction between specific residues is conserved, but the protonation events involve different residues compared to another type of spidroin. This suggests that the overall mechanism of pH-dependent dimerization is conserved but can be mediated by different pathways in different silk types.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Zigmantas Toleikis, Raitis Bobrovs, Agne Janoniene, Alons Lends, Mantas Ziaunys, Ieva Baronaite, Vytautas Petrauskas, Kristine Kitoka, Vytautas Smirnovas, Kristaps Jaudzems
Summary: S100A9 interacts with α-synuclein and influences the aggregation process. This study analyzed the interaction using F-19 and 2D N-15-H-1-HSQC NMR spectroscopy and studied the aggregation properties of these two proteins. The results showed that α-synuclein interacts with S100A9 at specific regions, which are also essential in the first step of aggregation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Olga Bobileva, Raitis Bobrovs, Evelina Elva Sirma, Iveta Kanepe, Anna L. Bula, Liene Patetko, Anna Ramata-Stunda, Solveiga Grinberga, Aigars Jirgensons, Kristaps Jaudzems
Summary: SARS-CoV-2 nsp14 guanine-N7-methyltransferase is crucial for viral RNA translation, and compound 5p was developed as a potent inhibitor targeting both SAM and mRNA-binding pockets of nsp14. It exhibited subnanomolar inhibitory activity and enhanced cell membrane permeability compared to the parent inhibitor, suggesting its potential as a bisubstrate inhibitor for further development in combating the virus.
Article
Biology
Alons Lends, Asen Daskalov, Ansis Maleckis, Aline Delamare, Melanie Berbon, Axelle Grelard, Estelle Morvan, Jayakrishna Shenoy, Antoine Dutour, James Tolchard, Abdelmajid Noubhani, Marie-France Giraud, Corinne Sanchez, Birgit Habenstein, Gilles Guichard, Guillaume Compain, Kristaps Jaudzems, Sven J. Saupe, Antoine Loquet
Summary: Structural investigations of amyloid fibrils often rely on heterologous bacterial overexpression of the protein of interest. Cell-free protein expression is a promising alternative to produce hydrophobic proteins and improve NMR analysis. In this study, the cell-free synthesis of the functional amyloid prion HET-s(218-289) was successfully implemented, and it was found that the protein directly assembles into infectious fibrils without denaturation and purification procedures. The cell-free synthesized amyloid fibrils can be analyzed using high-resolution magic-angle spinning NMR.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Diana Zelencova-Gopejenko, Melita Videja, Aiga Grandane, Linda Pudnika-Okincica, Anda Sipola, Karlis Vilks, Maija Dambrova, Kristaps Jaudzems, Edgars Liepinsh
Summary: Heart-type fatty-acid binding protein (FABP3) is a cytosolic lipid transport protein that binds fatty acids (FAs) and protects cells from the detrimental effects of long-chain acylcarnitines (LCACs). Through cytotoxicity assays, nuclear magnetic resonance, and isothermal titration calorimetry, the study characterizes the novel binding mechanism between FABP3 and LCACs. The findings demonstrate that FABP3 competes with FAs for binding sites and has a concentration-dependent protective mechanism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Felix Torres, Matthias Buetikofer, Gabriela R. R. Stadler, Alois Renn, Harindranath Kadavath, Raitis Bobrovs, Kristaps Jaudzems, Roland Riek
Summary: Although nuclear magnetic resonance (NMR) is commonly used in fragment-based drug design, its lack of sensitivity has limited its implementation in high-throughput screening. However, photochemically induced dynamic nuclear polarization (photo-CIDNP) is a promising method that can improve the sensitivity of NMR. This research demonstrates the detection of weak binders using low micromolar concentrations, exploiting the polarization enhancement provided by photo-CIDNP and achieving faster interaction detection compared to standard techniques. Furthermore, an automated flow-through platform and a photo-CIDNP fragment library are presented, providing a comprehensive approach for fragment-based screening.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
James Schiemer, Andrew Maxwell, Reto Horst, Shenping Liu, Daniel P. Uccello, Kris Borzilleri, Nisha Rajamohan, Matthew F. Brown, Matthew F. Calabrese
Summary: Targeted protein degradation using heterobifunctional chimeras can expand the druggable proteome and target proteins that are difficult to inhibit with small molecules. This study explores the role of covalent modification in targeted protein degradation using Bruton's tyrosine kinase, demonstrating its compatibility with the degradation mechanism.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Arenida Bartkeviciene, Aldona Jasukaitiene, Inga Zievyte, Darius Stukas, Sandra Ivanauskiene, Daiva Urboniene, Toivo Maimets, Kristaps Jaudzems, Astra Vitkauskiene, Jason Matthews, Zilvinas Dambrauskas, Antanas Gulbinas
Summary: This study found that the expression level of aryl-hydrocarbon receptor (AHR) plays a crucial role in immune dysregulation in pancreatic cancer, suggesting that it could be a potential target for early diagnostics and personalized therapeutics.
Article
Medical Laboratory Technology
Pavol Mikolka, Nina Kronqvist, Marie Haegerstrand-Bjorkman, Kristaps Jaudzems, Petra Kosutova, Maros Kolomaznik, Mihkel Saluri, Michael Landreh, Andrea Calkovska, Tore Curstedt, Jan Johansson
Summary: This study developed a novel surfactant called Combo that showed promising therapeutic effects in both premature and adult rabbit models of respiratory distress syndrome (RDS), which is caused by insufficient lung surfactant. Combo proved to be more resistant to inhibition and demonstrated better improvement in respiratory parameters compared to the natural-derived surfactant currently used in clinical practice for treating RDS. This makes Combo an attractive candidate for developing new therapies against human ARDS.
TRANSLATIONAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Rebecca L. L. Whitehouse, Wesam S. S. Alwan, Olga V. V. Ilyichova, Ashley J. J. Taylor, Indu R. R. Chandrashekaran, Biswaranjan Mohanty, Bradley C. C. Doak, Martin J. J. Scanlon
Summary: Fragment-based drug design relies on structural information obtained through X-ray crystallography to evolve fragments into lead-like compounds through structure-based design. The composition of compound libraries can be optimized to probe binding hot spots on protein surfaces.
RSC MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Tanguy Le Marchand, Tobias Schubeis, Marta Bonaccorsi, Piotr Paluch, Daniela Lalli, Andrew J. Pell, Loren B. Andreas, Kristaps Jaudzems, Jan Stanek, Guido Pintacuda
Summary: H-1-detected MAS NMR has become an efficient method for investigating biomolecular structure, dynamics, and interactions by solid-state NMR, with significant advancements in sensitivity and resolution.